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Sample records for oxidative therapeutic formulation

  1. Immunological effects of iron oxide nanoparticles and iron-based complex drug formulations: Therapeutic benefits, toxicity, mechanistic insights, and translational considerations.

    Science.gov (United States)

    Shah, Ankit; Dobrovolskaia, Marina A

    2018-04-01

    Nanotechnology offers several advantages for drug delivery. However, there is the need for addressing potential safety concerns regarding the adverse health effects of these unique materials. Some such effects may occur due to undesirable interactions between nanoparticles and the immune system, and they may include hypersensitivity reactions, immunosuppression, and immunostimulation. While strategies, models, and approaches for studying the immunological safety of various engineered nanoparticles, including metal oxides, have been covered in the current literature, little attention has been given to the interactions between iron oxide-based nanomaterials and various components of the immune system. Here we provide a comprehensive review of studies investigating the effects of iron oxides and iron-based nanoparticles on various types of immune cells, highlight current gaps in the understanding of the structure-activity relationships of these materials, and propose a framework for capturing their immunotoxicity to streamline comparative studies between various types of iron-based formulations. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Formulation and method for preparing gels comprising hydrous aluminum oxide

    Science.gov (United States)

    Collins, Jack L.

    2014-06-17

    Formulations useful for preparing hydrous aluminum oxide gels contain a metal salt including aluminum, an organic base, and a complexing agent. Methods for preparing gels containing hydrous aluminum oxide include heating a formulation to a temperature sufficient to induce gel formation, where the formulation contains a metal salt including aluminum, an organic base, and a complexing agent.

  3. Recommendations of the Oligonucleotide Safety Working Group's Formulated Oligonucleotide Subcommittee for the Safety Assessment of Formulated Oligonucleotide-Based Therapeutics.

    Science.gov (United States)

    Marlowe, Jennifer L; Akopian, Violetta; Karmali, Priya; Kornbrust, Douglas; Lockridge, Jennifer; Semple, Sean

    2017-08-01

    The use of lipid formulations has greatly improved the ability to effectively deliver oligonucleotides and has been instrumental in the rapid expansion of therapeutic development programs using oligonucleotide drugs. However, the development of such complex multicomponent therapeutics requires the implementation of unique, scientifically sound approaches to the nonclinical development of these drugs, based upon a hybrid of knowledge and experiences drawn from small molecule, protein, and oligonucleotide therapeutic drug development. The relative paucity of directly applicable regulatory guidance documents for oligonucleotide therapeutics in general has resulted in the generation of multiple white papers from oligonucleotide drug development experts and members of the Oligonucleotide Safety Working Group (OSWG). The members of the Formulated Oligonucleotide Subcommittee of the OSWG have utilized their collective experience working with a variety of formulations and their associated oligonucleotide payloads, as well as their insights into regulatory considerations and expectations, to generate a series of consensus recommendations for the pharmacokinetic characterization and nonclinical safety assessment of this unique class of therapeutics. It should be noted that the focus of Subcommittee discussions was on lipid nanoparticle and other types of particulate formulations of therapeutic oligonucleotides and not on conjugates or other types of modifications of oligonucleotide structure intended to facilitate delivery.

  4. Chemical modifications of therapeutic proteins induced by residual ethylene oxide.

    Science.gov (United States)

    Chen, Louise; Sloey, Christopher; Zhang, Zhongqi; Bondarenko, Pavel V; Kim, Hyojin; Ren, Da; Kanapuram, Sekhar

    2015-02-01

    Ethylene oxide (EtO) is widely used in sterilization of drug product primary containers and medical devices. The impact of residual EtO on protein therapeutics is of significant interest in the biopharmaceutical industry. The potential for EtO to modify individual amino acids in proteins has been previously reported. However, specific identification of EtO adducts in proteins and the effect of residual EtO on the stability of therapeutic proteins has not been reported to date. This paper describes studies of residual EtO with two therapeutic proteins, a PEGylated form of the recombinant human granulocyte colony-stimulating factor (Peg-GCSF) and recombinant human erythropoietin (EPO) formulated with human serum albumin (HSA). Peg-GCSF was filled in an EtO sterilized delivery device and incubated at accelerated stress conditions. Glu-C peptide mapping and LC-MS analyses revealed residual EtO reacted with Peg-GCSF and resulted in EtO modifications at two methionine residues (Met-127 and Met-138). In addition, tryptic peptide mapping and LC-MS analyses revealed residual EtO in plastic vials reacted with HSA in EPO formulation at Met-328 and Cys-34. This paper details the work conducted to understand the effects of residual EtO on the chemical stability of protein therapeutics. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  5. A comparison of the radiochemical stability of different iodine-131 labelled metaiodobenzylguanidine formulations for therapeutic use

    International Nuclear Information System (INIS)

    Wafelman, A.R.; Beijnen, J.H.; Hoefnagel, C.A.; Maes, R.A.A.

    1994-01-01

    The results of a stability study of three commercially available formulations of [ 131 I]MIBG for therapeutic use and an unstabilized formulation, stored under various conditions, are presented. The stability was followed for 20 days. In all formulations tested, free [ 131 I]iodide, formed by radiolysis, was the most important radiochemical impurity. The pharmaceutical formulation with the largest amount of stabilizer was radiochemically - but not chemically -most stable. (author)

  6. Applications of lipid based formulation technologies in the delivery of biotechnology-based therapeutics.

    Science.gov (United States)

    du Plessis, Lissinda H; Marais, Etienne B; Mohammed, Faruq; Kotzé, Awie F

    2014-01-01

    In the last decades several new biotechnologically-based therapeutics have been developed due to progress in genetic engineering. A growing challenge facing pharmaceutical scientists is formulating these compounds into oral dosage forms with adequate bioavailability. An increasingly popular approach to formulate biotechnology-based therapeutics is the use of lipid based formulation technologies. This review highlights the importance of lipid based drug delivery systems in the formulation of oral biotechnology based therapeutics including peptides, proteins, DNA, siRNA and vaccines. The different production procedures used to achieve high encapsulation efficiencies of the bioactives are discussed, as well as the factors influencing the choice of excipient. Lipid based colloidal drug delivery systems including liposomes and solid lipid nanoparticles are reviewed with a focus on recent advances and updates. We further describe microemulsions and self-emulsifying drug delivery systems and recent findings on bioactive delivery. We conclude the review with a few examples on novel lipid based formulation technologies.

  7. Multiphase layered oxide growth on pure metals. I. General formulation

    International Nuclear Information System (INIS)

    Fromhold, A.T. Jr.

    1982-01-01

    A general formulation for the simultaneous growth of any number of layered planar oxide phases on a pure metal under diffusion-controlled conditions has been developed. Four individual situations have been developed in detail, namely, situations in which the predominant mode of ion transport is by cation interstitials, cation vacancies, anion interstitials, or anion vacancies. The generalized formulation enables the determination of quasi-steady-state growth kinetics following step function changes in the experimental conditions such as ambient oxygen pressure or temperature. Numerical evaluation of the coupled growth equations for the individual phases is required to deduce the general predictions of the theory. In the limit of two-layer growth by cation interstitial diffusion, the present formulation reproduces the earlier results of Fromhold and Sato

  8. Solidified self-nanoemulsifying formulation for oral delivery of combinatorial therapeutic regimen

    DEFF Research Database (Denmark)

    Jain, Amit K; Thanki, Kaushik; Jain, Sanyog

    2014-01-01

    formulation in contrast to that of clinically available tamoxifen citrate when measured as function of hepatotoxicity markers and histopathological changes. CONCLUSIONS: In nutshell, co-encapsulation of quercetin with tamoxifen in solid SNEDDS poses great potential in improving the therapeutic efficacy...

  9. Written case formulations in the treatment of anorexia nervosa: Evidence for therapeutic benefits.

    Science.gov (United States)

    Allen, Karina L; O'Hara, Caitlin B; Bartholdy, Savani; Renwick, Beth; Keyes, Alexandra; Lose, Anna; Kenyon, Martha; DeJong, Hannah; Broadbent, Hannah; Loomes, Rachel; McClelland, Jessica; Serpell, Lucy; Richards, Lorna; Johnson-Sabine, Eric; Boughton, Nicky; Whitehead, Linette; Treasure, Janet; Wade, Tracey; Schmidt, Ulrike

    2016-09-01

    Case formulation is a core component of many psychotherapies and formulation letters may provide an opportunity to enhance the therapeutic alliance and improve treatment outcomes. This study aimed to determine if formulation letters predict treatment satisfaction, session attendance, and symptom reductions in anorexia nervosa (AN). It was hypothesized that higher quality formulation letters would predict greater treatment satisfaction, a greater number of attended sessions, and greater improvement in eating disorder symptoms. Patients were adult outpatients with AN (n = 46) who received Maudsley Anorexia Nervosa Treatment for Adults (MANTRA) in the context of a clinical trial. A Case Formulation Rating Scheme was used to rate letters for adherence to the MANTRA model and use of a collaborative, reflective, affirming stance. Analyses included linear regression and mixed models. Formulation letters that paid attention to the development of the AN predicted greater treatment acceptability ratings (p = 0.002). More reflective and respectful letters predicted greater reductions in Eating Disorder Examination scores (p = 0.003). Results highlight the potential significance of a particular style of written formulation as part of treatment for AN. Future research should examine applicability to other psychiatric disorders. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2016; 49:874-882). © 2016 Wiley Periodicals, Inc.

  10. Diabetic Neuropathy and Oxidative Stress: Therapeutic Perspectives

    Directory of Open Access Journals (Sweden)

    Asieh Hosseini

    2013-01-01

    Full Text Available Diabetic neuropathy (DN is a widespread disabling disorder comprising peripheral nerves' damage. DN develops on a background of hyperglycemia and an entangled metabolic imbalance, mainly oxidative stress. The majority of related pathways like polyol, advanced glycation end products, poly-ADP-ribose polymerase, hexosamine, and protein kinase c all originated from initial oxidative stress. To date, no absolute cure for DN has been defined; although some drugs are conventionally used, much more can be found if all pathophysiological links with oxidative stress would be taken into account. In this paper, although current therapies for DN have been reviewed, we have mainly focused on the links between DN and oxidative stress and therapies on the horizon, such as inhibitors of protein kinase C, aldose reductase, and advanced glycation. With reference to oxidative stress and the related pathways, the following new drugs are under study such as taurine, acetyl-L-carnitine, alpha lipoic acid, protein kinase C inhibitor (ruboxistaurin, aldose reductase inhibitors (fidarestat, epalrestat, ranirestat, advanced glycation end product inhibitors (benfotiamine, aspirin, aminoguanidine, the hexosamine pathway inhibitor (benfotiamine, inhibitor of poly ADP-ribose polymerase (nicotinamide, and angiotensin-converting enzyme inhibitor (trandolapril. The development of modern drugs to treat DN is a real challenge and needs intensive long-term comparative trials.

  11. Diabetic Neuropathy and Oxidative Stress: Therapeutic Perspectives

    Science.gov (United States)

    Hosseini, Asieh; Abdollahi, Mohammad

    2013-01-01

    Diabetic neuropathy (DN) is a widespread disabling disorder comprising peripheral nerves' damage. DN develops on a background of hyperglycemia and an entangled metabolic imbalance, mainly oxidative stress. The majority of related pathways like polyol, advanced glycation end products, poly-ADP-ribose polymerase, hexosamine, and protein kinase c all originated from initial oxidative stress. To date, no absolute cure for DN has been defined; although some drugs are conventionally used, much more can be found if all pathophysiological links with oxidative stress would be taken into account. In this paper, although current therapies for DN have been reviewed, we have mainly focused on the links between DN and oxidative stress and therapies on the horizon, such as inhibitors of protein kinase C, aldose reductase, and advanced glycation. With reference to oxidative stress and the related pathways, the following new drugs are under study such as taurine, acetyl-L-carnitine, alpha lipoic acid, protein kinase C inhibitor (ruboxistaurin), aldose reductase inhibitors (fidarestat, epalrestat, ranirestat), advanced glycation end product inhibitors (benfotiamine, aspirin, aminoguanidine), the hexosamine pathway inhibitor (benfotiamine), inhibitor of poly ADP-ribose polymerase (nicotinamide), and angiotensin-converting enzyme inhibitor (trandolapril). The development of modern drugs to treat DN is a real challenge and needs intensive long-term comparative trials. PMID:23738033

  12. Current Therapeutic Strategies for Adipose Tissue Defects/Repair Using Engineered Biomaterials and Biomolecule Formulations

    Directory of Open Access Journals (Sweden)

    Christopher M. Mahoney

    2018-05-01

    Full Text Available Tissue engineered scaffolds for adipose restoration/repair has significantly evolved in recent years. Patients requiring soft tissue reconstruction, caused by defects or pathology, require biomaterials that will restore void volume with new functional tissue. The gold standard of autologous fat grafting (AFG is not a reliable option. This review focuses on the latest therapeutic strategies for the treatment of adipose tissue defects using biomolecule formulations and delivery, and specifically engineered biomaterials. Additionally, the clinical need for reliable off-the-shelf therapies, animal models, and challenges facing current technologies are discussed.

  13. Current Therapeutic Strategies for Adipose Tissue Defects/Repair Using Engineered Biomaterials and Biomolecule Formulations.

    Science.gov (United States)

    Mahoney, Christopher M; Imbarlina, Cayla; Yates, Cecelia C; Marra, Kacey G

    2018-01-01

    Tissue engineered scaffolds for adipose restoration/repair has significantly evolved in recent years. Patients requiring soft tissue reconstruction, caused by defects or pathology, require biomaterials that will restore void volume with new functional tissue. The gold standard of autologous fat grafting (AFG) is not a reliable option. This review focuses on the latest therapeutic strategies for the treatment of adipose tissue defects using biomolecule formulations and delivery, and specifically engineered biomaterials. Additionally, the clinical need for reliable off-the-shelf therapies, animal models, and challenges facing current technologies are discussed.

  14. Recent Trends in Nanotechnology-Based Drugs and Formulations for Targeted Therapeutic Delivery.

    Science.gov (United States)

    Iqbal, Hafiz M N; Rodriguez, Angel M V; Khandia, Rekha; Munjal, Ashok; Dhama, Kuldeep

    2017-01-01

    In the recent past, a wider spectrum of nanotechnologybased drugs or drug-loaded devices and systems has been engineered and investigated with high interests. The key objective is to help for an enhanced/better quality of patient life in a secure way by avoiding/limiting drug abuse, or severe adverse effects of some in practice traditional therapies. Various methodological approaches including in vitro, in vivo, and ex vivo techniques have been exploited, so far. Among them, nanoparticles-based therapeutic agents are of supreme interests for an enhanced and efficient delivery in the current biomedical sector of the modern world. The development of new types of novel, effective and highly reliable therapeutic drug delivery system (DDS) for multipurpose applications is essential and a core demand to tackle many human health related diseases. In this context, nanotechnology-based several advanced DDS have been engineered with novel characteristics for biomedical, pharmaceutical and cosmeceutical applications that include but not limited to the enhanced/improved bioactivity, bioavailability, drug efficacy, targeted delivery, and therapeutically safer with an extra advantage of overcoming demerits of traditional drug formulations/designs. This review work is focused on recent trends/advances in nanotechnology-based drugs and formulations designed for targeted therapeutic delivery. Moreover, information is also reviewed and given from recent patents and summarized or illustrated diagrammatically to depict a better understanding. Recent patents covering various nanotechnology-based approaches for several applications have also been reviewed. The drug-loaded nanoparticles are among versatile candidates with multifunctional characteristics for potential applications in biomedical, and tissue engineering sector. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. Formulation and acoustic studies of a new phase-shift agent for diagnostic and therapeutic ultrasound.

    Science.gov (United States)

    Sheeran, Paul S; Luois, Samantha; Dayton, Paul A; Matsunaga, Terry O

    2011-09-06

    Recent efforts in the area of acoustic droplet vaporization with the objective of designing extravascular ultrasound contrast agents has led to the development of stabilized, lipid-encapsulated nanodroplets of the highly volatile compound decafluorobutane (DFB). We developed two methods of generating DFB droplets, the first of which involves condensing DFB gas (boiling point from -1.1 to -2 °C) followed by extrusion with a lipid formulation in HEPES buffer. Acoustic droplet vaporization of micrometer-sized lipid-coated droplets at diagnostic ultrasound frequencies and mechanical indices were confirmed optically. In our second formulation methodology, we demonstrate the formulation of submicrometer-sized lipid-coated nanodroplets based upon condensation of preformed microbubbles containing DFB. The droplets are routinely in the 200-300 nm range and yield microbubbles on the order of 1-5 μm once vaporized, consistent with ideal gas law expansion predictions. The simple and effective nature of this methodology allows for the development of a variety of different formulations that can be used for imaging, drug and gene delivery, and therapy. This study is the first to our knowledge to demonstrate both a method of generating ADV agents by microbubble condensation and formulation of primarily submicrometer droplets of decafluorobutane that remain stable at physiological temperatures. Finally, activation of DFB nanodroplets is demonstrated using pressures within the FDA guidelines for diagnostic imaging, which may minimize the potential for bioeffects in humans. This methodology offers a new means of developing extravascular contrast agents for diagnostic and therapeutic applications. © 2011 American Chemical Society

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

    Science.gov (United States)

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

    2015-06-01

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

  17. Therapeutic equivalence and pharmacokinetics of generic tacrolimus formulation in de novo kidney transplant patients.

    Science.gov (United States)

    Min, Sang-Il; Ha, Jongwon; Kim, Yon Su; Ahn, Sang Hyun; Park, Taejin; Park, Dae Do; Kim, Suh Min; Min, Seung-Kee; Hong, Hyejin; Ahn, Curie; Kim, Sang Joon

    2013-12-01

    There is a growing concern about the therapeutic equivalence of the generic tacrolimus formulation (GEN Tacrolimus) to the reference tacrolimus (REF Tacrolimus) in solid organ transplantation. A prospective, randomized study of 126 de novo renal transplant patients was conducted to compare the efficacy, safety and pharmacokinetic (PK) profiles between GEN tacrolimus (n = 63) and REF tacrolimus (n = 63). The PK of tacrolimus was evaluated on Day 10 and 6 months under steady-state condition. Crossover study was carried out in 66 patients at 6 months. On Day 10, 117 patients completed PK profiles (54 GEN tacrolimus and 63 REF tacrolimus) and GEN tacrolimus showed comparable C(0) (9.8 ± 2.5 versus 9.7 ± 3.0 ng/mL, P = 0.80) but significantly higher dose-normalized C(max) (309.1 ± 191.9 versus 192.5 ± 95.2 ng/mL/mg/kg, P PK profiles evaluated at 9 months showed that generic substitution also resulted in an 'early and high C(max)'. Efficacy and safety data were comparable over the 9-month study period. Therapeutic equivalence and the PK of GEN tacrolimus should be evaluated in patients undergoing de novo renal transplantation.

  18. 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.

  19. Thermal and oxidative degradation studies of formulated C-ethers by gel-permeation chromatography

    Science.gov (United States)

    Jones, W. R., Jr.; Morales, W.

    1982-01-01

    Gel-permeation chromatography was used to analyze C-ether lubricant formulations from high-temperature bearing tests and from micro-oxidation tests. Three mu-styragel columns (one 500 and two 100 A) and a tetrahydrofuran mobile phase were found to adequately separate the C-ether degradation products. The micro-oxidation tests yielded degradation results qualitatively similar to those observed from the bearing tests. Micro-oxidation tests conducted in air yielded more degradation than did tests in nitrogen. No great differences were observed between the thermal-oxidative stabilities of the two C-ether formulations or between the catalytic degradation activities of silver and M-50 steel. C-ether formulation I did yield more degradation than did formulation II in 111- and 25-hour bearing tests, respectively.

  20. Polymeric nanoparticles for co-delivery of synthetic long peptide antigen and poly IC as therapeutic cancer vaccine formulation

    NARCIS (Netherlands)

    Rahimian, Sima; Fransen, Marieke F.; Kleinovink, Jan Willem; Christensen, Jonatan Riis; Amidi, Maryam|info:eu-repo/dai/nl/304834912; Hennink, Wim E.|info:eu-repo/dai/nl/070880409; Ossendorp, Ferry

    2015-01-01

    The aim of the current study was to develop a cancer vaccine formulation for treatment of human papillomavirus (HPV)-induced malignancies. Synthetic long peptides (SLPs) derived from HPV16 E6 and E7 oncoproteins have been used for therapeutic vaccination in clinical trials with promising results. In

  1. A comprehensive linear programming tool to optimize formulations of ready-to-use therapeutic foods: An application to Ethiopia

    Science.gov (United States)

    Ready-to-use therapeutic food (RUTF) is the standard of care for children suffering from noncomplicated severe acute malnutrition (SAM). The objective was to develop a comprehensive linear programming (LP) tool to create novel RUTF formulations for Ethiopia. A systematic approach that surveyed inter...

  2. Case formulation and the therapeutic relationship: the role of therapist self-reflection and self-revelation.

    Science.gov (United States)

    Tufekcioglu, Sumru; Muran, J Christopher

    2015-05-01

    This article examines the role of the therapist's self-reflection and self-revelation in case formulation. We believe that a collaboratively constructed case formulation must always be considered in the context of an evolving therapeutic relationship. Further, self-reflection and self-revelation on the part of the therapist are critical for a more elaborate and nuanced case formulation and for understanding the patient. This highlights the importance of attunement to the here and now and the evolving therapeutic relationship. From this attunement, the therapist's self-reflection and self-revelation can emerge further, which can lead to the patient's personal growth and increased self-other awareness. To illustrate our point, we present an integrative, relational model in the case of a patient who has been in treatment. © 2015 Wiley Periodicals, Inc.

  3. Characterizing viscoelasticity of unhydrolyzed chicken sternal cartilage extract suspensions: Towards development of injectable therapeutics formulations.

    Science.gov (United States)

    Hama, Brian; Mahajan, Gautam; Kothapalli, Chandrasekhar

    2017-08-01

    Exogenous delivery of cartilage extract is being explored as a promising candidate for knee arthritis treatment as it biomimics native cartilage tissue characteristics. In this study, we report on the rheological characterization of aqueous suspensions constituted from a powdered form of unhydrolyzed chicken sternum extract. The effect of particle size (as-received vs. milled), suspension fluid (water vs. PBS), and temperature (37°C vs. 4°C), on the viscoelastic properties of the sternum extract based particulate suspensions were evaluated. Results showed that these suspensions exhibit shear-thinning characteristics as shear rate (γ̇) increases, while viscosity (η), storage (G'), and loss (G″) moduli of the suspensions increased with increasing particulate loading (ϕ: 2.5-10wt%). Reducing the as-received particle size by milling decreased G', G, and η of the suspensions and increased the influence of ϕ on these properties, possibly due to improved particle packing. Replacing water with PBS had no significant effect on the rheological properties, but temperature reduction from 37°C to 4°C increased G', G", and η of the suspensions and lowered the impact of powder loading on viscoelastic properties. The suspension's time-dependent response was typical of viscoelastic materials, characterized by an asymptotical approach to a final stress (stress relaxation) or strain (creep). Results were fit to a power-law model for creep, a general relaxation model for exponential decay in stress, Carreau-Yasuda models for flow curves, and a two-parameter Liu model to identify the maximum powder loading (ϕ m ). Among the various forces involved in particle-particle interactions within these suspensions, electrostatic forces appeared to dominate the most. Such characterization of the viscoelastic nature of these suspensions would help in formulating stable injectable cartilage extract based therapeutics for in vivo applications. Copyright © 2017 Elsevier Ltd. All

  4. Oxidation of urate by a therapeutic nitric oxide/air mixture

    International Nuclear Information System (INIS)

    Hicks, M.; Nguyen, L.; Day, R.; Rogers, P.

    1996-01-01

    Full text: Little is known about the potential toxicological consequences of therapeutic exposure of lung tissue to inhaled nitric oxide (NO). This route of administration is currently being successfully employed for the treatment of pulmonary hypertension and other lung pathologies including acute reperfusion injury in lung transplant patients. The toxicity of NO lies in its ability to act as an oxidant either in its own right or in concert with oxygen or with the superoxide free radical. One important interaction may be the reaction of these products with protective antioxidants in the lung epithelial lining fluid. One such antioxidant found in significant concentrations in both upper and lower airways is uric acid. In the present study, urate solutions (30μM) were exposed to a therapeutic concentration of NO gas, (35 ppm in air), for up to 90 minutes. Oxidative changes were followed spectrophotometrically and by HPLC. Significant loss of uric acid was observed with a concomitant formation of nitrite and allantoin, the stable oxidation product of NO and the major oxidation product of uric acid, respectively. No oxidation of urate was observed in the presence of air alone or when urate was incubated with nitrite. Uric acid oxidation could also be prevented by passing the NO / air stream through 10% KOH before the uric acid solution. This strategy removed trace amounts of higher oxides of nitrogen, (especially NO 2 ), from the NO / air stream. Thus, therapeutic inhalation of NO may deplete soluble antioxidants such as uric acid, especially during long-term chronic exposure unless care is taken to minimise formation of higher oxides of nitrogen

  5. Potential therapeutic effect of nanobased formulation of rivastigmine on rat model of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Ismail MF

    2013-01-01

    Full Text Available Manal Fouad Ismail,1 Aliaa Nabil ElMeshad,2 Neveen Abdel-Hameed Salem31Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 3Department of Narcotics and Ergogenic Aids and Poisons, National Research Center, Giza, EgyptBackground: To sustain the effect of rivastigmine, a hydrophilic cholinesterase inhibitor, nanobased formulations were prepared. The efficacy of the prepared rivastigmine liposomes (RLs in comparison to rivastigmine solution (RS was assessed in an aluminium chloride (AlCl3-induced Alzheimer’s model.Methods: Liposomes were prepared by lipid hydration (F1 and heating (F2 methods. Rats were treated with either RS or RLs (1 mg/kg/day concomitantly with AlCl3 (50 mg/kg/day.Results: The study showed that the F1 method produced smaller liposomes (67.51 ± 14.2 nm than F2 (528.7 ± 15.5 nm, but both entrapped the same amount of the drug (92.1% ± 1.4%. After 6 hours, 74.2% ± 1.5% and 60.8% ± 2.3% of rivastigmine were released from F1 and F2, respectively. Both RLs and RS improved the deterioration of spatial memory induced by AlCl3, with RLs having a superior effect. Further biochemical measurements proved that RS and RLs were able to lower plasma C-reactive protein, homocysteine and asymmetric dimethylarginine levels. RS significantly attenuated acetylcholinesterase (AChE activity, whereas Na+/K+-adenosine triphosphatase (ATPase activity was enhanced compared to the AlCl3-treated animals; however, RLs succeeded in normalization of AChE and Na+/K+ ATPase activities. Gene-expression profile showed that cotreatment with RS to AlCl3-treated rats succeeded in exerting significant decreases in BACE1, AChE, and IL1B gene expression. Normalization of the expression of the aforementioned genes was achieved by coadministration of RLs to AlCl3-treated rats. The profound therapeutic effect of RLs over RS was

  6. Formulation, functional evaluation and ex vivo performance of thermoresponsive soluble gels - A platform for therapeutic delivery to mucosal sinus tissue.

    Science.gov (United States)

    Pandey, Preeti; Cabot, Peter J; Wallwork, Benjamin; Panizza, Benedict J; Parekh, Harendra S

    2017-01-01

    Mucoadhesive in situ gelling systems (soluble gels) have received considerable attention recently as effective stimuli-transforming vectors for a range of drug delivery applications. Considering this fact, the present work involves systematic formulation development, optimization, functional evaluation and ex vivo performance of thermosensitive soluble gels containing dexamethasone 21-phosphate disodium salt (DXN) as the model therapeutic. A series of in situ gel-forming systems comprising the thermoreversible polymer poloxamer-407 (P407), along with hydroxypropyl methyl cellulose (HPMC) and chitosan were first formulated. The optimized soluble gels were evaluated for their potential to promote greater retention at the mucosal surface, for improved therapeutic efficacy, compared to existing solution/suspension-based steroid formulations used clinically. Optimized soluble gels demonstrated a desirable gelation temperature with Newtonian fluid behaviour observed under storage conditions (4-8°C), and pseudoplastic fluid behaviour recorded at nasal cavity/sinus temperature (≈34°C). The in vitro characterization of formulations including rheological evaluation, textural analysis and mucoadhesion studies of the gel form were investigated. Considerable improvement in mechanical properties and mucoadhesion was observed with incorporation of HPMC and chitosan into the gelling systems. The lead poloxamer-based soluble gels, PGHC4 and PGHC7, which were carried through to ex vivo permeation studies displayed extended drug release profiles in conditions mimicking the human nasal cavity, which indicates their suitability for treating a range of conditions affecting the nasal cavity/sinuses. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Investigation of Lipid Oxidation in the Raw Materials of a Topical Skin Formulation: A Topical Skin Formulation Containing a High Lipid Content

    DEFF Research Database (Denmark)

    Thomsen, Birgitte Raagaard; Taylor, Richard; Madsen, Robert

    2018-01-01

    Several studies have demonstrated that lipid oxidation often occurs in topical skin formulations which can affect product odor (both positively and negatively). Furthermore, odor detection threshold values and odor descriptors of identified volatile oxidation products in cleansing and skin cream...... formulation prototypes were recently determined by a trained sensory panel at the Technical University of Denmark in the Division of Food Technology. In this study, we investigated lipid oxidation in a prototype skin cream formulation as well as in selected cosmetic skin care raw materials. Lipid oxidation...... was also identified. In addition, the concentrations of several well-known lipid oxidation products increased during storage and were suggested to originate primarily from rice bran wax, which oxidized more readily than other raw materials due to its unsaturated nature....

  8. Modified tricalcium silicate cement formulations with added zirconium oxide.

    Science.gov (United States)

    Li, Xin; Yoshihara, Kumiko; De Munck, Jan; Cokic, Stevan; Pongprueksa, Pong; Putzeys, Eveline; Pedano, Mariano; Chen, Zhi; Van Landuyt, Kirsten; Van Meerbeek, Bart

    2017-04-01

    This study aims to investigate the effect of modifying tricalcium silicate (TCS) cements on three key properties by adding ZrO 2 . TCS powders were prepared by adding ZrO 2 at six different concentrations. The powders were mixed with 1 M CaCl 2 solution at a 3:1 weight ratio. Biodentine (contains 5 wt.% ZrO 2 ) served as control. To evaluate the potential effect on mechanical properties, the mini-fracture toughness (mini-FT) was measured. Regarding bioactivity, Ca release was assessed using ICP-AES. The component distribution within the cement matrix was evaluated by Feg-SEM/EPMA. Cytotoxicity was assessed using an XTT assay. Adding ZrO 2 to TCS did not alter the mini-FT (p = 0.52), which remained in range of that of Biodentine (p = 0.31). Ca release from TSC cements was slightly lower than that from Biodentine at 1 day (p > 0.05). After 1 week, Ca release from TCS 30 and TCS 50 increased to a level that was significantly higher than that from Biodentine (p  0.05). EPMA revealed a more even distribution of ZrO 2 within the TCS cements. Particles with an un-reacted core were surrounded by a hydration zone. The 24-, 48-, and 72-h extracts of TCS 50 were the least cytotoxic. ZrO 2 can be added to TCS without affecting the mini-FT; Ca release was reduced initially, to reach a prolonged release thereafter; adding ZrO 2 made TCS cements more biocompatible. TCS 50 is a promising cement formulation to serve as a biocompatible hydraulic calcium silicate cement.

  9. Oxidative Stress and Liver Cancer: Etiology and Therapeutic Targets

    Directory of Open Access Journals (Sweden)

    Zhanpeng Wang

    2016-01-01

    Full Text Available Accumulating evidence has indicated that oxidative stress (OS is associated with the development of hepatocellular carcinoma (HCC. However, the mechanisms remain largely unknown. Normally, OS occurs when the body receives any danger signal—from either an internal or external source—and further induces DNA oxidative damage and abnormal protein expression, placing the body into a state of vulnerability to the development of various diseases such as cancer. There are many factors involved in liver carcinogenesis, including hepatitis B virus (HBV and hepatitis C virus (HCV infection, alcohol abuse, and nonalcoholic fatty liver disease (NAFLD. The relationship between OS and HCC has recently been attracting increasing attention. Therefore, elucidation of the impact of OS on the development of liver carcinogenesis is very important for the prevention and treatment of liver cancer. This review focuses mainly on the relationship between OS and the development of HCC from the perspective of cellular and molecular mechanisms and the etiology and therapeutic targets of HCC.

  10. Solidified self-nanoemulsifying formulation for oral delivery of combinatorial therapeutic regimen

    DEFF Research Database (Denmark)

    Jain, Amit K; Thanki, Kaushik; Jain, Sanyog

    2014-01-01

    PURPOSE: The present work reports rationalized development and characterization of solidified self-nanoemulsifying drug delivery system for oral delivery of combinatorial (tamoxifen and quercetin) therapeutic regimen. METHODS: Suitable oil for the preparation of liquid SNEDDS was selected based...

  11. In vivo effects of traditional Ayurvedic formulations in Drosophila melanogaster model relate with therapeutic applications.

    Directory of Open Access Journals (Sweden)

    Vibha Dwivedi

    Full Text Available Ayurveda represents the traditional medicine system of India. Since mechanistic details of therapy in terms of current biology are not available in Ayurvedic literature, modern scientific studies are necessary to understand its major concepts and procedures. It is necessary to examine effects of the whole Ayurvedic formulations rather than their "active" components as is done in most current studies.We tested two different categories of formulations, a Rasayana (Amalaki Rasayana or AR, an herbal derivative and a Bhasma (Rasa-Sindoor or RS, an organo-metallic derivative of mercury, for effects on longevity, development, fecundity, stress-tolerance, and heterogeneous nuclear ribonucleoprotein (hnRNP levels of Drosophila melanogaster using at least 200 larvae or flies for each assay.A 0.5% (weight/volume supplement of AR or RS affected life-history and other physiological traits in distinct ways. While the size of salivary glands, hnRNP levels in larval tissues, and thermotolerance of larvae/adult flies improved significantly following feeding either of the two formulations, the median life span and starvation resistance improved only with AR. Feeding on AR or RS supplemented food improved fecundity differently. Feeding of larvae and adults with AR increased the fecundity while the same with RS had opposite effect. On the contrary, feeding larvae on normal food and adults on AR supplement had no effect on fecundity but a comparable regime of feeding on RS-supplemented food improved fecundity. RS feeding did not cause heavy metal toxicity.The present study with two Ayurvedic formulations reveals formulation-specific effects on several parameters of the fly's life, which seem to generally agree with their recommended human usages in Ayurvedic practices. Thus, Drosophila, with its very rich genetic tools and well-worked-out developmental pathways promises to be a very good model for examining the cellular and molecular bases of the effects of

  12. A comprehensive linear programming tool to optimize formulations of ready-to-use therapeutic foods: an application to Ethiopia.

    Science.gov (United States)

    Ryan, Kelsey N; Adams, Katherine P; Vosti, Stephen A; Ordiz, M Isabel; Cimo, Elizabeth D; Manary, Mark J

    2014-12-01

    Ready-to-use therapeutic food (RUTF) is the standard of care for children suffering from noncomplicated severe acute malnutrition (SAM). The objective was to develop a comprehensive linear programming (LP) tool to create novel RUTF formulations for Ethiopia. A systematic approach that surveyed international and national crop and animal food databases was used to create a global and local candidate ingredient database. The database included information about each ingredient regarding nutrient composition, ingredient category, regional availability, and food safety, processing, and price. An LP tool was then designed to compose novel RUTF formulations. For the example case of Ethiopia, the objective was to minimize the ingredient cost of RUTF; the decision variables were ingredient weights and the extent of use of locally available ingredients, and the constraints were nutritional and product-quality related. Of the new RUTF formulations found by the LP tool for Ethiopia, 32 were predicted to be feasible for creating a paste, and these were prepared in the laboratory. Palatable final formulations contained a variety of ingredients, including fish, different dairy powders, and various seeds, grains, and legumes. Nearly all of the macronutrient values calculated by the LP tool differed by <10% from results produced by laboratory analyses, but the LP tool consistently underestimated total energy. The LP tool can be used to develop new RUTF formulations that make more use of locally available ingredients. This tool has the potential to lead to production of a variety of low-cost RUTF formulations that meet international standards and thereby potentially allow more children to be treated for SAM. © 2014 American Society for Nutrition.

  13. Characterization of absorption enhancers for orally administered therapeutic peptides in tablet formulations - Applying statistical learning

    DEFF Research Database (Denmark)

    Welling, Søren Havelund

    . In the Caco-2 model all reagents are pre-dissolved, and therefore the assay cannot predict critical solubility issues and bile salt interactions in the final tablet formulation. A QSAR solubility model was built to foresee and avoid slow tablet dissolution. Due to enzyme kinetics, slow tablet dissolution...

  14. Zinc oxide as a new antimicrobial preservative of topical products: interactions with common formulation ingredients.

    Science.gov (United States)

    Pasquet, Julia; Chevalier, Yves; Couval, Emmanuelle; Bouvier, Dominique; Bolzinger, Marie-Alexandrine

    2015-02-01

    Zinc oxide (ZnO) appears as a promising preservative for pharmaceutical or cosmetic formulations. The other ingredients of the formulations may have specific interactions with ZnO that alter its antimicrobial properties. The influence of common formulation excipients on the antimicrobial efficacy of ZnO has been investigated in simple model systems and in typical topical products containing a complex formulation. A wide variety of formulation excipients have been investigated for their interactions with ZnO: antioxidants, chelating agents, electrolytes, titanium dioxide pigment. The antimicrobial activity of ZnO against Escherichia coli was partially inhibited by NaCl and MgSO4 salts. A synergistic influence of uncoated titanium dioxide has been observed. The interference effects of antioxidants and chelating agents were quite specific. The interactions of these substances with ZnO particles and with the soluble species released by ZnO were discussed so as to reach scientific guidelines for the choice of the ingredients. The preservative efficacy of ZnO was assessed by challenge testing in three different formulations: an oil-in-water emulsion; a water-in-oil emulsion and a dry powder. The addition of ZnO in complex formulations significantly improved the microbiological quality of the products, in spite of the presence of other ingredients that modulate the antimicrobial activity. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Differential modulation of nitric oxide synthases in aging: therapeutic opportunities

    Directory of Open Access Journals (Sweden)

    Stêfany Bruno De Assis Cau

    2012-06-01

    Full Text Available Vascular aging is the term that describes the structural and functional disturbances of the vasculature with advancing aging. The molecular mechanisms of aging-associated endothelial dysfunction are complex, but reduced nitric oxide (NO bioavailability and altered vascular expression and activity of NO synthase (NOS enzymes have been implicated as major players. Impaired vascular relaxation in aging has been attributed to reduced endothelial NOS (eNOS-derived NO, while increased inducible NOS (iNOS expression seems to account for nitrosative stress and disrupted vascular homeostasis. Although eNOS is considered the main source of NO in the vascular endothelium, neuronal NOS (nNOS also contributes to endothelial cells-derived NO, a mechanism that is reduced in aging. Pharmacological modulation of NO generation and expression/activity of NOS isoforms may represent a therapeutic alternative to prevent the progression of cardiovascular diseases. Accordingly, this review will focus on drugs that modulate NO bioavailability, such as nitrite anions and NO-releasing non-steroidal anti-inflammatory drugs, hormones (dehydroepiandrosterone and estrogen, statins, resveratrol and folic acid, since they may be useful to treat/to prevent aging-associated vascular dysfunction. The impact of these therapies on life quality in elderly and longevity will be discussed.

  16. Formulation of Synthesized Zinc Oxide Nanopowder into Hybrid Beads for Dye Separation

    Directory of Open Access Journals (Sweden)

    H. Shokry Hassan

    2014-01-01

    Full Text Available The sol-gel prepared zinc oxide nanopowder was immobilized onto alginate-polyvinyl alcohol polymer blend to fabricate novel biocomposite beads. Various physicochemical characterization techniques have been utilized to identify the crystalline, morphological, and chemical structures of both the fabricated zinc oxide hybrid beads and their corresponding zinc oxide nanopowder. The thermal stability investigations demonstrate that ZnO nanopowder stability dramatically decreased with its immobilization into the polymeric alginate and PVA matrix. The formulated beads had very strong mechanical strength and they are difficult to be broken up to 1500 rpm. Moreover, these hybrid beads are chemically stable at the acidic media (pH < 7 especially within the pH range of 2–7. Finally, the applicability of the formulated ZnO hybrid beads for C.I. basic blue 41 (BB41 decolorization from aqueous solution was examined.

  17. NEW THERAPEUTIC FORMULATIONS WITH AN ANTIBACTERIAL EFFECT, BASED ON PLANT EXTRACTS

    Directory of Open Access Journals (Sweden)

    Liliana Cristina Soare

    2012-12-01

    Full Text Available The antibacterial effects produced by anthocyanins and other bioactive plant compounds are weaker than those generated by antibiotics. In some cases, the combination of extract-antibiotic can cause synergistic effects, also the purpose of the research was to develop and test new antibiotic - plant extract formulations. New potential antimicrobial formulations was done by soaking discs impregnated with piperacillin or tetracycline with different extract. The tested microorganisms were: Staphylococcus aureus ATCC 25923, Streptococcus sp., Escherichia coli 820B, soil bacterium 23S, and Enterobacter cloacae. The combination of antibiotics with extracts determined, only for some of the microorganisms tested, better antibacterial effects than those caused by the antibiotic or the extract.

  18. Therapeutic evaluation of grain based functional food formulation in a geriatric animal model.

    Science.gov (United States)

    Teradal, Deepa; Joshi, Neena; Aladakatti, Ravindranath H

    2017-08-01

    This study investigates the effect of wholesome grain based functional food formulation, on clinical and biochemical parameters in 24-30 months old Wistar albino geriatric rats, corresponding to human age 60-75 years. Animals were randomly divided into five, groups. Experimental diets were compared to the basal rat diet (Group I). Four food, formulation were-wheat based (Group II), finger millet based (Group III), wheat based, diet + fenugreek seed powder (Group IV), finger millet based diet + fenugreek powder, (Group V). These five types of diets were fed to the experimental rats for 6 weeks. Hematological and biochemical parameters were evaluated. The results showed that, feed intake was influenced by the type of feed. Diets supplemented with, fenugreek (Group IV) caused a significant increase in serum hemoglobin. The total serum protein values were significantly highest in Group III. Total serum albumin was found to be lower in Group I and highest in Group II. The concentration of BUN was highest in Group I and the lowest in control diet. Serum cholesterol and glucose were significantly reduced in Group IV. Several hematological and serum mineral values were influenced by the type of diet. The type of diet did not influence the organs weight. A moderate hypoglycemic and hypercholesterolemic effect was observed in composite mix fed rats. This study clearly justifies the recommendation to use wholesome grain based functional foods for geriatric population.

  19. Dissolution of synthetic uranium dibutyl phosphate deposits in oxidizing and reducing chemical formulations

    International Nuclear Information System (INIS)

    Rufus, A.L.; Sathyaseelan, V.S.; Narasimhan, S.V.; Velmurugan, S.

    2013-01-01

    Graphical abstract: SEM of the U-DBP coated stainless steel coupon before and after exposure to chemical formulation containing acid permanganate at 80 °C. -- Highlights: •Combination of oxidation and reduction processes efficiently dissolves U-DBP deposits. •NP and NAC formulations are compatible with SS-304. •Dissolved uranium and added chemicals are effectively removed via ion exchangers. -- Abstract: Permanganate and nitrilotriacetic acid (NTA) based dilute chemical formulations were evaluated for the dissolution of uranium dibutyl phosphate (U-DBP), a compound that deposits over the surfaces of nuclear reprocessing plants and waste storage tanks. A combination of an acidic, oxidizing treatment (nitric acid with permanganate) followed by reducing treatment (NTA based formulation) efficiently dissolved the U-DBP deposits. The dissolution isotherm of U-DBP in its as precipitated form followed a logarithmic fit. The same chemical treatment was also effective in dissolving U-DBP coated on the surface of 304-stainless steel, while resulting in minimal corrosion of the stainless steel substrate material. Investigation of uranium recovery from the resulting decontamination solutions by ion exchange with a bed of mixed anion and cation resins showed quantitative removal of uranium

  20. Dissolution of synthetic uranium dibutyl phosphate deposits in oxidizing and reducing chemical formulations

    Energy Technology Data Exchange (ETDEWEB)

    Rufus, A.L.; Sathyaseelan, V.S.; Narasimhan, S.V.; Velmurugan, S., E-mail: svelu@igcar.gov.in

    2013-06-15

    Graphical abstract: SEM of the U-DBP coated stainless steel coupon before and after exposure to chemical formulation containing acid permanganate at 80 °C. -- Highlights: •Combination of oxidation and reduction processes efficiently dissolves U-DBP deposits. •NP and NAC formulations are compatible with SS-304. •Dissolved uranium and added chemicals are effectively removed via ion exchangers. -- Abstract: Permanganate and nitrilotriacetic acid (NTA) based dilute chemical formulations were evaluated for the dissolution of uranium dibutyl phosphate (U-DBP), a compound that deposits over the surfaces of nuclear reprocessing plants and waste storage tanks. A combination of an acidic, oxidizing treatment (nitric acid with permanganate) followed by reducing treatment (NTA based formulation) efficiently dissolved the U-DBP deposits. The dissolution isotherm of U-DBP in its as precipitated form followed a logarithmic fit. The same chemical treatment was also effective in dissolving U-DBP coated on the surface of 304-stainless steel, while resulting in minimal corrosion of the stainless steel substrate material. Investigation of uranium recovery from the resulting decontamination solutions by ion exchange with a bed of mixed anion and cation resins showed quantitative removal of uranium.

  1. Green Synthesis of Formulated Zinc Oxide Nanoparticles for Chemical Protection of Skin Care and Related Applications

    Science.gov (United States)

    Koppolu, Ramya

    Nanomaterials have diversified applications based on the unique properties. These nanoparticles and functionalized nanocomposites have been studied in the health care filed. Nanoparticles are mostly used in sunscreens which are a part of human life. These sunscreens consist of titanium dioxide and zinc oxide nanoparticles. Due to the higher band crevices, they help the skin to protect from ultraviolet rays, for instance, ultraviolet B and ultraviolet A. A series of nanostructured zinc oxide nanoparticles were prepared by cost-effective chemical and bioinspired methods and variables were optimized. Highly stable and spherical zinc oxide nanoparticles were formulated by aloe vera ( Aloe barbadensis) plant extract and avocado (Persea americana Mill) fruit extract. The state-of-the-art instrumentation was used to characterize the morphology, elemental composition, and particle size distribution. X-ray diffraction data indicated highly crystalline and ultrafine nanoparticles were obtained from the colloidal methods. The X-ray photoelectron spectroscopy results showed the chemical state of zinc, carbon, and oxygen atoms were well-indexed and are used as fingerprint identification of the elements. Transmission electron microscopy images show the shape of particles were cubic and fiber shape contingent upon the protecting operators and heat treatment conditions. The toxicity studies of zinc oxide nanoparticles were found to cause an increase in nitric oxide, which is protecting against further oxidative stress and appears to be nontoxic.

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Sean M Bell

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

  4. Ginseng essence, a medicinal and edible herbal formulation, ameliorates carbon tetrachloride-induced oxidative stress and liver injury in rats

    Directory of Open Access Journals (Sweden)

    Kuan-Hung Lu

    2017-07-01

    Conclusion: These findings demonstrate that GE improves CCl4-induced liver inflammation and fibrosis by attenuating oxidative stress. Therefore, GE could be a promising hepatoprotective herbal formulation for future development of phytotherapy.

  5. Therapeutic strategies to address neuronal nitric oxide synthase deficiency and the loss of nitric oxide bioavailability in Duchenne Muscular Dystrophy.

    Science.gov (United States)

    Timpani, Cara A; Hayes, Alan; Rybalka, Emma

    2017-05-25

    Duchenne Muscular Dystrophy is a rare and fatal neuromuscular disease in which the absence of dystrophin from the muscle membrane induces a secondary loss of neuronal nitric oxide synthase and the muscles capacity for endogenous nitric oxide synthesis. Since nitric oxide is a potent regulator of skeletal muscle metabolism, mass, function and regeneration, the loss of nitric oxide bioavailability is likely a key contributor to the chronic pathological wasting evident in Duchenne Muscular Dystrophy. As such, various therapeutic interventions to re-establish either the neuronal nitric oxide synthase protein deficit or the consequential loss of nitric oxide synthesis and bioavailability have been investigated in both animal models of Duchenne Muscular Dystrophy and in human clinical trials. Notably, the efficacy of these interventions are varied and not always translatable from animal model to human patients, highlighting a complex interplay of factors which determine the downstream modulatory effects of nitric oxide. We review these studies herein.

  6. Nitric Oxide Manipulation: A Therapeutic Target for Peripheral Arterial Disease?

    Directory of Open Access Journals (Sweden)

    Gareth Williams

    2012-01-01

    Full Text Available Peripheral Arterial Disease (PAD is a cause of significant morbidity and mortality in the Western world. Risk factor modification and endovascular and surgical revascularisation are the main treatment options at present. However, a significant number of patients still require major amputation. There is evidence that nitric oxide (NO and its endogenous inhibitor asymmetric dimethylarginine (ADMA play significant roles in the pathophysiology of PAD. This paper reviews experimental work implicating the ADMA-DDAH-NO pathway in PAD, focussing on both the vascular dysfunction and effects within the ischaemic muscle, and examines the potential of manipulating this pathway as a novel adjunct therapy in PAD.

  7. 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

  8. Oxidative Stress in Neurodegenerative Diseases: Mechanisms and Therapeutic Perspectives

    Directory of Open Access Journals (Sweden)

    Ailton Melo

    2011-01-01

    Full Text Available The incidence and prevalence of neurodegenerative diseases (ND increase with life expectancy. This paper reviews the role of oxidative stress (OS in ND and pharmacological attempts to fight against reactive oxygen species (ROS-induced neurodegeneration. Several mechanisms involved in ROS generation in neurodegeneration have been proposed. Recent articles about molecular pathways involved in ROS generation were reviewed. The progress in the development of neuroprotective therapies has been hampered because it is difficult to define targets for treatment and determine what should be considered as neuroprotective. Therefore, the attention was focused on researches about pharmacological targets that could protect neurons against OS. Since it is necessary to look for genes as the ultimate controllers of all biological processes, this paper also tried to identify gerontogenes involved in OS and neurodegeneration. Since neurons depend on glial cells to survive, recent articles about the functioning of these cells in aging and ND were also reviewed. Finally, clinical trials testing potential neuroprotective agents were critically reviewed. Although several potential drugs have been screened in in vitro and in vivo models of ND, these results were not translated in benefit of patients, and disappointing results were obtained in the majority of clinical trials.

  9. Poly herbal formulation with anti-elastase and anti-oxidant properties for skin anti-aging.

    Science.gov (United States)

    Kalyana Sundaram, Induja; Sarangi, Deepika Deeptirekha; Sundararajan, Vignesh; George, Shinomol; Sheik Mohideen, Sahabudeen

    2018-01-29

    Skin forms an important part of human innate immune system. Wrinkles, thinning and roughening of skin are some of the symptoms that affect the skin as it ages. Reactive oxygen species induced oxidative stress plays a major role in skin aging by modulating the elastase enzyme level in the skin. Extrinsic factors that affect skin aging such as UV radiation can also cause malignant melanoma. Here we selected four medicinal plant materials, namely, leaves of Nyctanthes arbor-tristis, unripe and ripe Aegle marmelos fruit pulp and the terminal meristem of Musa paradisiaca flower and investigated their anti-aging properties and cytotoxicity in vitro individually as well as in a poly herbal formulation containing the four plant extracts in different ratios. The phytochemical contents of the plant extracts were investigated for radical scavenging activity and total reducing power. Based upon its anti-oxidant properties, a poly herbal formulation containing leaves of Nyctanthes arbor-tristis, unripe and ripe fruit pulp of Aegle marmelos, and the terminal meristem of Musa paradisiaca flower in the ratio 6:2:1:1 (Poly Herbal Formulation 1) and 1:1:1:1 (Poly Herbal Formulation 2), respectively were formulated. It has been observed that the Poly Herbal Formulation 1 was more potent than Poly Herbal Formulation 2 due to better anti-oxidant and anti-elastase activities in NIH3T3 fibroblast cells. In addition Poly Herbal formulation 1 also had better anti-cancer activity in human malignant melanoma cells. Based on these results these beneficial plant extracts were identified for its potential application as an anti-aging agent in skin creams as well as an anti-proliferation compound against cancer cells.

  10. Harnessing insulin- and leptin-induced oxidation of PTP1B for therapeutic development.

    Science.gov (United States)

    Krishnan, Navasona; Bonham, Christopher A; Rus, Ioana A; Shrestha, Om Kumar; Gauss, Carla M; Haque, Aftabul; Tocilj, Ante; Joshua-Tor, Leemor; Tonks, Nicholas K

    2018-01-18

    The protein tyrosine phosphatase PTP1B is a major regulator of glucose homeostasis and energy metabolism, and a validated target for therapeutic intervention in diabetes and obesity. Nevertheless, it is a challenging target for inhibitor development. Previously, we generated a recombinant antibody (scFv45) that recognizes selectively the oxidized, inactive conformation of PTP1B. Here, we provide a molecular basis for its interaction with reversibly oxidized PTP1B. Furthermore, we have identified a small molecule inhibitor that mimics the effects of scFv45. Our data provide proof-of-concept that stabilization of PTP1B in an inactive, oxidized conformation by small molecules can promote insulin and leptin signaling. This work illustrates a novel paradigm for inhibiting the signaling function of PTP1B that may be exploited for therapeutic intervention in diabetes and obesity.

  11. Determination of Ideal Broth Formulations Needed to Prepare Hydrous Cerium Oxide Microspheres via the Internal Gelation Process

    Energy Technology Data Exchange (ETDEWEB)

    Collins, Jack Lee [ORNL; Chi, Anthony [ORNL

    2009-02-01

    A simple test tube methodology was used to determine optimum process parameters for preparing hydrous cerium oxide microspheres via the internal gelation process.1 Broth formulations of cerium ammonium nitrate [(NH4)2Ce(NO3)6], hexamethylenetetramine, and urea were found that can be used to prepare hydrous cerium oxide gel spheres in the temperature range of 60 to 90 C. A few gel-forming runs were made in which microspheres were prepared with some of these formulations to be able to equate the test-tube gelation times to actual gelation times. These preparations confirmed that the test-tube methodology is reliable for determining the ideal broth formulations.

  12. 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.

  13. Electrochemical oxidation of amoxicillin in its pharmaceutical formulation at boron doped diamond (BDD electrode

    Directory of Open Access Journals (Sweden)

    Corneil Quand-Meme Gnamba

    2015-08-01

    Full Text Available In this work, voltammetric andelectrolysis experiments have been carried out on a conductive boron dopeddiamond (BDD electrode in solution containing amoxicillin in itspharmaceutical formulation. The physical characterization of the BDD surface byscanning electron microscopy (SEM reveals a polycrystalline structure withgrain sizes ranging between 0.3 and 0.6 µm. With Raman spectroscopy, BDDsurface is composed of diamons (Csp3 type carbon (Csp3and graphitic type carbon (Csp2. The electrochemical characterization of the BDD electrode in sulfuric acid electrolyte showed a wide potential window worthing 2.74 V. The oxidation of Amoxicillin showed an irreversible anodic wave on the voltammogram in the domain of water stability indicating a direct oxidation of amoxicillin at BDD surface. The treatment of Amoxicillin in the synthetic wastewaters under various constant current densities 20, 50, 100, 135 mA cm-2 on BDD showed that Amoxicillin is highly reducedunder 100 mA cm-2 reaching 92% of the Chemical Oxygen Demand (CODremoval after 5 h of electrolysis. Investigation performed in perchloric acidas supporting electrolyte led to 87% of COD removal after 5 h of electrolysis.Mineralization of amoxicillin occurs on BDD and the chemical oxygen demandremoval was higher in sulfuric acid than in perchloric acid owing to theinvolvement of the in-situ formed persulfate and perchlorate  to the degradation process mainly in the bulkof the solution. The instantaneous current efficiency (ICE presents anexponential decay indicating that the process was limited by diffusion. Thespecific energy consumed after 5h of the amoxicillin electrolysis was 0.096 kWh COD-1and 0.035 kWh COD-1 in sulfuric acid and in perchloric acidrespectively.

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

    Science.gov (United States)

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

    2015-01-01

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

  15. Nitric oxide nanoparticles: Pre-clinical utility as a therapeutic for intramuscular abscesses

    OpenAIRE

    Schairer, David O.; Martinez, Luis R.; Blecher, Karin; Chouake, Jason S.; Nacharaju, Parimala; Gialanella, Philip; Friedman, Joel M.; Nosanchuk, Joshua D.; Friedman, Adam J.

    2012-01-01

    Nitric oxide (NO) is a critical component of host defense against invading pathogens; however, its therapeutic utility is limited due to a lack of practical delivery systems. Recently, a NO-releasing nanoparticulate platform (NO-np) was shown to have in vitro broad-spectrum antimicrobial activity and in vivo pre-clinical efficacy in a dermal abscess model. To extend these findings, both topical (TP) and intralesional (IL) NO-np administration was evaluated in a MRSA intramuscular murine absce...

  16. Mechanisms and consequences of oxidative stress in lung disease: therapeutic implications for an aging populace.

    Science.gov (United States)

    Hecker, Louise

    2018-04-01

    The rapid expansion of the elderly population has led to the recent epidemic of age-related diseases, including increased incidence and mortality of chronic and acute lung diseases. Numerous studies have implicated aging and oxidative stress in the pathogenesis of various pulmonary diseases; however, despite recent advances in these fields, the specific contributions of aging and oxidative stress remain elusive. This review will discuss the consequences of aging on lung morphology and physiology, and how redox imbalance with aging contributes to lung disease susceptibility. Here, we focus on three lung diseases for which aging is a significant risk factor: acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). Preclinical and clinical development for redox- and senescence-altering therapeutic strategies are discussed, as well as scientific advancements that may direct current and future therapeutic development. A deeper understanding of how aging impacts normal lung function, redox balance, and injury-repair processes will inspire the development of new therapies to prevent and/or reverse age-associated pulmonary diseases, and ultimately increase health span and longevity. This review is intended to encourage basic, clinical, and translational research that will bridge knowledge gaps at the intersection of aging, oxidative stress, and lung disease to fuel the development of more effective therapeutic strategies for lung diseases that disproportionately afflict the elderly.

  17. Human Growth Hormone Delivery with a Microneedle Transdermal System: Preclinical Formulation, Stability, Delivery and PK of Therapeutically Relevant Doses

    Directory of Open Access Journals (Sweden)

    Mahmoud Ameri

    2014-05-01

    Full Text Available This study evaluated the feasibility of coating formulated recombinant human growth hormone (rhGH on a titanium microneedle transdermal delivery system, Zosano Pharma (ZP-hGH, and assessed preclinical patch delivery performance. Formulation rheology and surface activity were assessed by viscometry and contact angle measurement. rhGH liquid formulation was coated onto titanium microneedles by dip-coating and drying. The stability of coated rhGH was determined by size exclusion chromatography-high performance liquid chromatography (SEC-HPLC. Preclinical delivery and pharmacokinetic studies were conducted in female hairless guinea pigs (HGP using rhGH coated microneedle patches at 0.5 and 1 mg doses and compared to Norditropin® a commercially approved rhGH subcutaneous injection. Studies demonstrated successful rhGH formulation development and coating on microneedle arrays. The ZP-hGH patches remained stable at 40 °C for six months with no significant change in % aggregates. Pharmacokinetic studies showed that the rhGH-coated microneedle patches, delivered with high efficiency and the doses delivered indicated linearity with average Tmax of 30 min. The absolute bioavailability of the microneedle rhGH patches was similar to subcutaneous Norditropin® injections. These results suggest that ZP-transdermal microneedle patch delivery of rhGH is feasible and may offer an effective and patient-friendly alternative to currently marketed rhGH injectables.

  18. Human Growth Hormone Delivery with a Microneedle Transdermal System: Preclinical Formulation, Stability, Delivery and PK of Therapeutically Relevant Doses.

    Science.gov (United States)

    Ameri, Mahmoud; Kadkhodayan, Miryam; Nguyen, Joe; Bravo, Joseph A; Su, Rebeca; Chan, Kenneth; Samiee, Ahmad; Daddona, Peter E

    2014-05-15

    This study evaluated the feasibility of coating formulated recombinant human growth hormone (rhGH) on a titanium microneedle transdermal delivery system, Zosano Pharma (ZP)-hGH, and assessed preclinical patch delivery performance. Formulation rheology and surface activity were assessed by viscometry and contact angle measurement. rhGH liquid formulation was coated onto titanium microneedles by dip-coating and drying. The stability of coated rhGH was determined by size exclusion chromatography-high performance liquid chromatography (SEC-HPLC). Preclinical delivery and pharmacokinetic studies were conducted in female hairless guinea pigs (HGP) using rhGH coated microneedle patches at 0.5 and 1 mg doses and compared to Norditropin® a commercially approved rhGH subcutaneous injection. Studies demonstrated successful rhGH formulation development and coating on microneedle arrays. The ZP-hGH patches remained stable at 40 °C for six months with no significant change in % aggregates. Pharmacokinetic studies showed that the rhGH-coated microneedle patches, delivered with high efficiency and the doses delivered indicated linearity with average Tmax of 30 min. The absolute bioavailability of the microneedle rhGH patches was similar to subcutaneous Norditropin® injections. These results suggest that ZP-transdermal microneedle patch delivery of rhGH is feasible and may offer an effective and patient-friendly alternative to currently marketed rhGH injectables.

  19. Investigation of Lipid Oxidation in High- and Low-Lipid-Containing Topical Skin Formulations

    DEFF Research Database (Denmark)

    Raagaard Thomsen, Birgitte; Frisenfeldt Horn, Anna; Hyldig, G.

    2017-01-01

    in the skin care formulations (especially during exposure to light), whereas in the lip care formulations the best candidates were pentanal (especially during exposure to light and iron), 2-methyl furan and 3-methyl-3-buten-2-one (especially during exposure to light, iron and high temperatures). Graphical...... Abstract: [Figure not available: see fulltext.]...

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

    Science.gov (United States)

    2014-01-01

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

  1. Platelet lysate mucohadesive formulation to treat oral mucositis in graft versus host disease patients: a new therapeutic approach.

    Science.gov (United States)

    Del Fante, Claudia; Perotti, Cesare; Bonferoni, Maria Cristina; Rossi, Silvia; Sandri, Giuseppina; Ferrari, Franca; Scudeller, Luigia; Caramella, Carla Marcella

    2011-09-01

    Optimal treatment of oral mucositis (OM) due to graft versus host disease (GvHD) is currently not available. Platelet-derived growth factors (PDGFs) have high capability for tissue healing and may play a role in repairing the mucosal barrier. The aim of the present work was to develop a mucoadhesive formulation to administer platelet lysate to oral cavity prolonging contact time of platelet lysate with oral mucosa. The mucoadhesive formulation was characterized for in vitro properties (PDGF-AB concentration, mucoadhesive properties, cytotoxicity, fibroblast proliferation, wound healing). Moreover, a preliminary clinical study on seven GvHD patients with OM refractory to other therapies was conducted, to evaluate feasibility, safety, and efficacy. GVPL (mucoadhesive gel vehicle mixed with platelet lysate)showed good mucoadhesive properties; additionally, it was characterized by good biocompatibility in vitro on fibroblasts and it was able to enhance fibroblast proliferation and wound healing, maintaining the efficacy for up to 14 days following storage at 2-8°C. In vivo, clinical response was good-to-complete in five, fair in one, none in the remaining one. The in vitro results indicate that GVPL has optimal mucoadhesive and healing enhancer properties, maintained over time (up to 14 days); preliminary clinical results suggest that oral application of platelet lysate-loaded mucoadhesive formulation is feasible, safe, well tolerated, and effective. A larger controlled randomized study is needed.

  2. 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.

  3. Application of a high-throughput relative chemical stability assay to screen therapeutic protein formulations by assessment of conformational stability and correlation to aggregation propensity.

    Science.gov (United States)

    Rizzo, Joseph M; Shi, Shuai; Li, Yunsong; Semple, Andrew; Esposito, Jessica J; Yu, Shenjiang; Richardson, Daisy; Antochshuk, Valentyn; Shameem, Mohammed

    2015-05-01

    In this study, an automated high-throughput relative chemical stability (RCS) assay was developed in which various therapeutic proteins were assessed to determine stability based on the resistance to denaturation post introduction to a chaotrope titration. Detection mechanisms of both intrinsic fluorescence and near UV circular dichroism (near-UV CD) are demonstrated. Assay robustness was investigated by comparing multiple independent assays and achieving r(2) values >0.95 for curve overlays. The complete reversibility of the assay was demonstrated by intrinsic fluorescence, near-UV CD, and biologic potency. To highlight the method utility, we compared the RCS assay with differential scanning calorimetry and dynamic scanning fluorimetry methodologies. Utilizing C1/2 values obtained from the RCS assay, formulation rank-ordering of 12 different mAb formulations was performed. The prediction of long-term stability on protein aggregation is obtained by demonstrating a good correlation with an r(2) of 0.83 between RCS and empirical aggregation propensity data. RCS promises to be an extremely useful tool to aid in candidate formulation development efforts based on the complete reversibility of the method to allow for multiple assessments without protein loss and the strong correlation between the C1/2 data obtained and accelerated stability under stressed conditions. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  4. The role of oxidative stress in Huntington's disease: are antioxidants good therapeutic candidates?

    Science.gov (United States)

    Gil-Mohapel, Joana; Brocardo, Patricia S; Christie, Brian R

    2014-04-01

    Huntington's disease (HD) is the most common polyglutamine neurodegenerative disorder in humans, and is caused by a mutation of an unstable expansion of CAG repeats within the coding region of the HD gene, which expresses the protein huntingtin. Although abnormal protein is ubiquitously expressed throughout the organism, cell degeneration occurs mainly in the brain, and there, predominantly in the striatum and cortex. The mechanisms that account for this selective neuronal death are multifaceted in nature and several lines of evidence suggest that mitochondrial dysfunction, overproduction of reactive oxygen species (ROS) and oxidative stress (an imbalance between pro-oxidant and antioxidant systems resulting in oxidative damage to proteins, lipids and DNA) might play important roles. Over time, this can result in the death of the affected neuronal populations. In this review article we present an overview of the preclinical and clinical studies that have indicated a link between oxidative stress, neurodegeneration, and cell death in HD. We also discuss how changes in ROS production affect neuronal survival, highlighting the evidence for the use of antioxidants including essential fatty acids, coenzyme Q10, and creatine, as potential therapeutic strategies for the treatment of this devastating neurodegenerative disorder.

  5. Evaluation of therapeutic potential of VB-001, a leave-on formulation, for the treatment of moderate adherent dandruff.

    Science.gov (United States)

    Bhattacharyya, Anamika; Jain, Nilu; Prasad, Sudhanand; Jain, Shilpi; Yadav, Vishal; Ghosh, Shamik; Sengupta, Shiladitya

    2017-05-03

    Dandruff is a common scalp condition characterized by excessive scaling and itch. Aberrant colonization of the scalp by commensal Malassezia spp. is a major contributor in the multifactorial etiology of dandruff. Literature based understanding of Malassezia linked pathophysiology of dandruff allowed us to comprehend a strategy to potentiate the efficacy of a known antifungal agent used in dandruff therapy. The aim of this study was to determine the efficacy and skin safety of VB-001 antidandruff leave-on formulation in comparison with marketed antidandruff ZPTO shampoo in patients with moderate adherent dandruff of the scalp. Healthy males or females aged ≥ 15 years and ≤ 65 with a clinical diagnosis of moderate adherent dandruff of the scalp were recruited for the study to monitor the effects of topical VB-001 versus those of marketed antidandruff ZPTO shampoo. 168 subjects were randomized to the treatment (VB-001, n = 84) and control (ZPTO shampoo, n = 84) groups. The efficacy of each product was evaluated by comparing proportion of subjects who have shown reduction in flaking by ASFS (adherent scalp flaking score) and pruritus by IGA (investigator global assessment) score. VB-001 imparted consistently better reduction in ASFS and enabled early reduction of pruritus in comparison to marketed ZPTO shampoo. VB-001, a leave-on formulation with ingredients chosen to selectively disturb the Malassezia niche on dandruff scalp by denying extra nutritional benefits to the microbe, provides unique advantages over existing best in class ZPTO shampoo therapy. It has the potential to emerge as an attractive novel treatment for moderate adherent dandruff. CTRI Registration number: CTRI/2013/01/003283 . Registered on: 02/01/2013.

  6. NanoDisk containing super aggregated amphotericin B: a high therapeutic index antifungal formulation with enhanced potency

    Directory of Open Access Journals (Sweden)

    Burgess BL

    2013-12-01

    Full Text Available Braydon L Burgess,1,2 Yumin He,1 Mandie M Baker,1,2 Bing Luo,2 Stephen F Carroll,2 Trudy M Forte,2 Michael N Oda11Children's Hospital Oakland Research Institute, Oakland, CA, USA; 2Lypro Biosciences, Berkeley, CA, USAObjectives: NanoDisk–amphotericin B (ND-AMB is a protein-phospholipid bioparticle containing a “super aggregate” form of antifungal AMB. While lipid-based formulations of AMB, including liposomal AMB (L-AMB, are safer than the deoxycholate (DOC solubilized form (DOC-AMB, the potency of lipid-based formulations is attenuated. We have developed an AMB-based therapy that is both well tolerated and fully efficacious.Methods: Potency was determined using broth culture growth-inhibition assays and candidacidal kinetics by quantitative culture plating. Toxicology studies were performed in healthy mice. Efficacy was assessed using both immune-competent and leukopenic murine models of systemic Candida albicans infection.Results: ND-AMB C. albicans and Aspergillus fumigatus minimum inhibitory concentrations were fourfold and sixfold lower, respectively, than that observed for L-AMB. ND-AMB exhibited candidacidal activity at 0.125 mg/L, 16-fold lower than L-AMB. In mice, ND-AMB produced no statistically significant kidney or liver toxicity at 15 mg/kg, the highest dose tested. When evaluated in immune-competent mice infected with C. albicans, ND-AMB was at least as effective as DOC-AMB or L-AMB. In a leukopenic model of candidiasis, the 50% effective dose of ND-AMB was around threefold lower than L-AMB.Conclusion: These results indicate that ND-AMB exhibits a more favorable safety profile while maintaining uncompromised antifungal properties compared to both DOC-AMB and L-AMB. ND-AMB is a promising therapy for the treatment of invasive fungal infections.Keywords: nanoparticles, infectious diseases, drug delivery, candidiasis, apolipoprotein A-I

  7. The nitric oxide prodrug JS-K and its structural analogues as cancer therapeutic agents.

    Science.gov (United States)

    Maciag, Anna E; Saavedra, Joseph E; Chakrapani, Harinath

    2009-09-01

    Nitric oxide (NO) prodrugs of the diazeniumdiolate class are routinely used as reliable sources of nitric oxide in chemical and biological laboratory settings. O(2)-(2,4-dinitrophenyl) diazeniumdiolates, which are derivatized forms of ionic diazeniumdiolates, have been found to show potent anti-proliferative activity in a variety of cancer cells, presumably through the effects of NO. One important member of this class of diazeniumdiolates, O(2)-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K), has shown promise as a novel cancer therapeutic agent in a number of animal models. This review describes the developments in chemical and biochemical characterization and structure-activity relationship of JS-K and its analogues. In addition, some molecular mechanistic insights into the observed anti-proliferative activity of JS-K are discussed. Finally, a structural motif is presented for O(2)-(aryl) diazeniumdiolate nitric oxide prodrugs that show potency comparable with that of JS-K.

  8. Oxidizing gel formulation for nuclear decontamination: rheological and acidic properties of the organic matrix and its ozonolysis

    International Nuclear Information System (INIS)

    Rouy, E.

    2003-10-01

    An acidic and oxidizing gel was formulated with a purely organic matrix, xanthan gum, at low concentrations (1 to 2 wt %). This polymer gel was investigated in various media (aqueous, acidic and ceric) by means of rheology: shear thinning behaviour, thixotropy, yield stress... Evidences of unexpected rheological properties in highly concentrated media show that xanthan is quite convenient for industrial projection of this type of gel on metallic walls in nuclear plants, notwithstanding its time-limited resistance to oxidation (about a few hours). Complexation mechanisms between ceric species and polar sites of the polymer led us to characterise acidic properties of our xanthan sample by potentiometric titration and 1 H NMR techniques. The matrix was finally treated by ozonolysis to suppress organic residues, as required to handle nuclear wastes. In acidic medium, ozonolysis of the gel was achieved successfully while in acidic and ceric medium this process showed limited efficiency, needing further investigation to be clarified. (author)

  9. Bulk Scale Formulation of Therapeutic Doses of Clinical Grade Ready-to-Use 177Lu-DOTA-TATE: The Intricate Radiochemistry Aspects.

    Science.gov (United States)

    Mathur, Anupam; Prashant, Vrinda; Sakhare, Navin; Chakraborty, Sudipta; Vimalnath, K V; Mohan, Repaka Krishna; Arjun, Chanda; Karkhanis, Barkha; Seshan, Ravi; Basu, Sandip; Korde, Aruna; Banerjee, Sharmila; Dash, Ashutosh; Sachdev, Satbir Singh

    2017-09-01

    177 Lu-DOTA-TATE is a clinically useful and promising therapeutic radiopharmaceutical for peptide receptor radionuclide therapy of neuroendocrine tumors (NETs) overexpressing somatostatin receptors. Currently, the radiopharmaceutical is prepared in-house at nuclear medicine centers, thereby restricting its use to limited centers only. In this article, the authors describe systematic studies toward bulk scale formulation of "ready-to-use" 177 Lu-DOTA-TATE using medium specific activity 177 Lu (740-1110 GBq/mg) at a centralized radiopharmacy facility. In an optimized protocol, 177 Lu-DOTA-TATE synthesis was carried out by direct heating of 177 LuCl 3 (Sp. act. 740-1110 GBq/mg) with DOTA-TATE peptide (1.5-3.0 equivalents) in ammonium acetate buffer (0.2 M) containing 2,5-dihydroxy benzoic acid (gentisic acid). Thereafter, the crude labeled product was purified using a Sep-Pak ® C18 column and diluted with acetate buffer-gentisic acid (1.5% w/v) solution to final radioactive concentration of 740 MBq/mL. This was further sterilized and dispensed as 7.4 GBq patient dose/vial with 2 days postformulation calibration. A peptide/metal ratio of 1.5-3.0 is essential for complexation wherein radiolabeling yields >90% are obtained minimizing free 177 Lu waste. For formulation of 7.4 GBq patient dose (2 days postproduction), even specific activity of about 555 GBq/mg was found to be adequate for the radiometal. The ready-to-use 740 MBq/mL 177 Lu-DOTA-TATE formulation with gentisic acid (1.5% w/v) is observed to be safe for human use for more than 1 week (radiochemical purity >98%) from the day of production when stored at -70°C. However, the target specificity may get affected beyond 2 days as the total peptide content for 7.4 GBq dose may exceed the critical peptide limit of 300 μg. Patient treatment carried with several batches of present formulation in diseased NET patients exhibited desired distribution at the tumor and its metastatic site. A ready

  10. Enhancement of the efficacy of therapeutic proteins by formulation with PEGylated liposomes; a case of FVIII, FVIIa and G-CSF.

    Science.gov (United States)

    Yatuv, Rivka; Robinson, Micah; Dayan, Inbal; Baru, Moshe

    2010-02-01

    Improving the pharmacodynamics of protein drugs has the potential to improve the care and the quality of life of patients suffering from a variety of diseases. Four approaches to improve protein drugs are described: PEGylation, amino acid substitution, fusion to carrier proteins and encapsulation. A new platform technology based on the binding of proteins/peptides to the outer surface of PEGylated liposomes (PEGLip) is then presented. Binding of proteins to PEGLip is non-covalent, highly specific and dependent on an amino acid consensus sequence within the proteins. Association of proteins with PEGLip results in substantial enhancement of the pharmacodynamic properties of proteins following administration. This has been demonstrated in preclinical studies and clinical trials with coagulation factors VIII and VIIa. It has also been demonstrated in preclinical studies with granulocyte colony-stimulating factor. A mechanism is presented that explains the improvements in hemostatic efficacy of PEGLip-formulated coagulation factors VIII and VIIa. The reader will gain an understanding of the advantages and disadvantages of each of the approaches discussed. PEGLip formulation is an important new approach to improve the pharmacodynamics of protein drugs. This approach may be applied to further therapeutic proteins in the future.

  11. Therapeutic potential of novel formulated forms of curcumin in the treatment of breast cancer by the targeting of cellular and physiological dysregulated pathways.

    Science.gov (United States)

    Tajbakhsh, Amir; Hasanzadeh, Malihe; Rezaee, Mehdi; Khedri, Mostafa; Khazaei, Majid; ShahidSales, Soodabeh; Ferns, Gordon A; Hassanian, Seyed Mahdi; Avan, Amir

    2018-03-01

    Breast cancer is among the most important causes of cancer related death in women. There is a need for novel agents for targeting key signaling pathways to either improve the efficacy of the current therapy, or reduce toxicity. There is some evidence that curcumin may have antitumor activity in breast cancer. Several clinical trials have investigated its activity in patients with breast cancer, including a recent trial in breast cancer patients receiving radiotherapy, in whom it was shown that curcumin reduced the severity of radiation dermatitis, although it is associated with low bioavailability. Several approaches have been developed to increase its absorption rate (e.g., nano crystals, liposomes, polymers, and micelles) and co-delivery of curcumin with adjuvants as well as different conjugation to enhance its bioavailability. In particular, micro-emulsions is an option for transdermal curcumin delivery, which has been reported to increase its absorption. Lipid-based nano-micelles is another approach to enhance curcumin absorption via gastrointestinal tract, while polymer-based nano-formulations (e.g., poly D, L-lactic-co-glycolic [PLGA]) allows the release of curcumin at a sustained level. This review summarizes the current data of the therapeutic potential of novel formulations of curcumin with particular emphasis on recent preclinical and clinical studies in the treatment of breast cancer. © 2017 Wiley Periodicals, Inc.

  12. Cytotoxic effects of oxytetracycline residues in the bones of broiler chickens following therapeutic oral administration of a water formulation.

    Science.gov (United States)

    Odore, R; De Marco, M; Gasco, L; Rotolo, L; Meucci, V; Palatucci, A T; Rubino, V; Ruggiero, G; Canello, S; Guidetti, G; Centenaro, S; Quarantelli, A; Terrazzano, G; Schiavone, A

    2015-08-01

    Tetracyclines, which represent one of the most commonly used antibiotics for poultry, are known to be deposited in bones, where they can remain, despite the observation of appropriate withdrawal times. The aim of the study was to determine the concentration of oxytretracycline (OTC) residues in the bone and muscle of chickens, following the oral administration of a commercially available liquid formulation, and to test their cytotoxic effects on an in vitro cell culture model. Seventy-two 1-day-old broiler chickens were randomly allotted into 2 groups (control and treated animals). OTC (40 mg/kg BW) was administered via drinking water during the 1 to 5 and 20 to 25 days of life periods. At the end of the trial, the birds were slaughtered and the OTC residues in the target tissues were measured by means of liquid chromatography (LC) - tandem mass spectrometry (MS/MS). Cytotoxicity was assessed by evaluating the pro-apoptotic effect of the bone residues on the K562 erythroleukemic line and on the peripheral blood mononuclear cells (PBMC). In all the animals, the OTC residues in the muscle were far below the established MRL of 100 μg/kg. The OTC levels in the bones of the treated animals were instead found in the parts per million (ppm) range. Cell cytotoxicity was assessed by evaluating the pro-apoptotic effect of OTC bone residues on the haematopoietic cell system. This in vitro system has revealed a significant pro-apoptotic effect on both the K562 cell line and PBMC cultures. This result suggests potential human and animal health risks due to the entry of tetracycline residues contained in the bones of treated livestock into the food-chain. This could be of concern, particularly for canine and feline diets, as meat, bone meal, and poultry by-products represent some of the main ingredients of pet foods, especially in the case of dry pet food. Further studies are needed to define the underlying mechanisms of cytotoxicity and to evaluate the in vivo toxicological

  13. A novel antioxidant formulation designed to treat male infertility associated with oxidative stress: promising preclinical evidence from animal models.

    Science.gov (United States)

    Gharagozloo, P; Gutiérrez-Adán, A; Champroux, A; Noblanc, A; Kocer, A; Calle, A; Pérez-Cerezales, S; Pericuesta, E; Polhemus, A; Moazamian, A; Drevet, J R; Aitken, R J

    2016-02-01

    Does a novel antioxidant formulation designed to restore redox balance within the male reproductive tract, reduce sperm DNA damage and increase pregnancy rates in mouse models of sperm oxidative stress? Oral administration of a novel antioxidant formulation significantly reduced sperm DNA damage in glutathione peroxidase 5 (GPX5), knockout mice and restored pregnancy rates to near-normal levels in mice subjected to scrotal heat stress. Animal and human studies have documented the adverse effect of sperm DNA damage on fertilization rates, embryo quality, miscarriage rates and the transfer of de novo mutations to offspring. Semen samples of infertile men are known to be deficient in several key antioxidants relative to their fertile counterparts. Antioxidants alone or in combination have demonstrated limited efficacy against sperm oxidative stress and DNA damage in numerous human clinical trials, however these studies have not been definitive and an optimum combination has remained elusive. The efficacy of the antioxidant formulation was evaluated in two well-established mouse models of oxidative stress, scrotal heating and Gpx5 knockout (KO) mice, (n = 12 per experimental group), by two independent laboratories. Mice were provided the antioxidant product in their drinking water for 2-8 weeks and compared with control groups for sperm DNA damage and pregnancy rates. In the Gpx5 KO model, oxidative DNA damage was monitored in spermatozoa by immunocytochemical detection of 8-hydroxy-2'-deoxyguanosine (8OHdG). In the scrotal heat stress model, male fertility was tested by partnering with three females for 5 days. The percentage of pregnant females, number of vaginal plugs, resorptions per litter, and litter size were recorded. Using immunocytochemical detection of 8OHdG as a biomarker of DNA oxidation, analysis of control mice revealed that around 30% of the sperm population was positively stained. This level increased to about 60% in transgenic mice deficient in the

  14. Nanoencapsulation of Rose-Hip Oil Prevents Oil Oxidation and Allows Obtainment of Gel and Film Topical Formulations.

    Science.gov (United States)

    Contri, Renata V; Kulkamp-Guerreiro, Irene C; da Silva, Sheila Janine; Frank, Luiza A; Pohlmann, Adriana R; Guterres, Silvia S

    2016-08-01

    The rose-hip oil holds skin regenerating properties with applications in the dermatological and cosmetic area. Its nanoencapsulation might favor the oil stability and its incorporation into hydrophilic formulations, besides increasing the contact with the skin and prolonging its effect. The aim of the present investigation was to develop suitable rose-hip-oil-loaded nanocapsules, to verify the nanocapsule effect on the UV-induced oxidation of the oil and to obtain topical formulations by the incorporation of the nanocapsules into chitosan gel and film. The rose-hip oil (500 or 600 μL), polymer (Eudragit RS100®, 100 or 200 mg), and acetone (50 or 100 mL) contents were separately varied aiming to obtain an adequate size distribution. The results led to a combination of the factors acetone and oil. The developed formulation showed average diameter of 158 ± 6 nm with low polydispersity, pH of 5.8 ± 0.9, zeta potential of +9.8 ± 1.5 mV, rose-hip oil content of 54 ± 1 μL/mL and tendency to reversible creaming. No differences were observed in the nanocapsules properties after storage. The nanoencapsulation of rose-hip oil decreased the UVA and UVC oxidation of the oil. The chitosan gel and film containing rose-hip-oil-loaded nanocapsules showed suitable properties for cutaneous use. In conclusion, it was possible to successfully obtain rose-hip-oil-loaded nanocapsules and to confirm the nanocapsules effect in protecting the oil from the UV rays. The chitosan gel and film were considered interesting alternatives for incorporating the nanoencapsulated rose-hip oil, combining the advantages of the nanoparticles to the advantages of chitosan.

  15. Novel nitric oxide generating compound glycidyl nitrate enhances the therapeutic efficacy of chemotherapy and radiotherapy.

    Science.gov (United States)

    Ning, Shoucheng; Bednarski, Mark; Oronsky, Bryan; Scicinski, Jan; Knox, Susan J

    2014-05-09

    Selective release of nitric oxide (NO) in tumors could improve the tumor blood flow and drug delivery for chemotherapeutic agents and radiotherapy, thereby increasing the therapeutic index. Glycidyl nitrate (GLYN) is a NO generating small molecule, and has ability to release NO on bioactivation in SCC VII tumor cells. GLYN-induced intracellular NO generation was significantly attenuated by NO scavenger carboxy-PTIO (cPTIO) and NAC. GLYN significantly increases tumor blood flow, but has no effect on the blood flow of normal tissues in tumor-bearing mice. When used with cisplatin, GLYN significantly increased the tumor growth inhibition effect of cisplatin. GLYN also had a modest radiosensitizing effect in vitro and in vivo. GLYN was well tolerated and there were no acute toxicities found at its effective therapeutic doses in preclinical studies. These results suggest that GLYN is a promising new drug for use with chemotherapy and radiotherapy, and provide a compelling rationale for future studies of GLYN and related compounds. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Bioactivation antioxidant and transglycating properties of N-acetylcarnosine autoinduction prodrug of a dipeptide L-carnosine in mucoadhesive drug delivery eye-drop formulation: powerful eye health application technique and therapeutic platform.

    Science.gov (United States)

    Babizhayev, Mark A

    2012-06-01

    A considerable interest in N-acetylcarnosine ocular drug design for eye health is based on clinical strategies to improve ocular drug delivery through metabolic enzymatic activation. Human biology aspects of ocular N-acetylcarnosine deacetylation during its pass through the cornea to the aqueous humor and dipeptide hydrolyzing enzymes are characterized. Novel approaches to ocular drug delivery increasing intraocular bioavailability of N-acetylcarnosine biologically activated metabolite carnosine become an integral development ensuring prolonged retention of the medication in the mucoadhesive precorneal area and facilitating transcorneal penetration of the natural dipeptide with the corneal promoters. A comprehensive list of techniques for peptide drug design, synthesis, purification, and biological analyses was considered: liquid chromatography (LC), high performance liquid chromatography (HPLC), (1) H and (13) C nuclear magnetic resonance (NMR), electrospray ionization (ESI) mass spectroscopy, and spectrophotometry. The antioxidant activity of therapeutics-targeted molecules was studied in aqueous solution and in a lipid membrane environment. A deglycation therapeutic system was developed involving removal, by transglycation of sugar or aldehyde moieties from Schiff bases by histidyl-hydrazide compounds or aldehyde scavenger L-carnosine. Clinical studies included ophthalmoscopy, visual acuity (VA), halometer disability glare tests, slit-image, and retro-illumination photography. N-acetylcarnosine 1% lubricant eye drops are considered as an auto-induction prodrug and natural ocular redox state balance therapies with implications in prevention and treatment of serious eye diseases that involve pathways of continuous oxidative damage to ocular tissues(cataracts, primary open-angle glaucoma, age-related macular degeneration) and sight-threatening glycosylation processes (diabetic retinopathy and consequent visual impairment) important for public health. The results of

  17. 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.

  18. HbE/β-Thalassemia and Oxidative Stress: The Key to Pathophysiological Mechanisms and Novel Therapeutics.

    Science.gov (United States)

    Hirsch, Rhoda Elison; Sibmooh, Nathawut; Fucharoen, Suthat; Friedman, Joel M

    2017-05-10

    Oxidative stress and generation of free radicals are fundamental in initiating pathophysiological mechanisms leading to an inflammatory cascade resulting in high rates of morbidity and death from many inherited point mutation-derived hemoglobinopathies. Hemoglobin (Hb)E is the most common point mutation worldwide. The β E -globin gene is found in greatest frequency in Southeast Asia, including Thailand, Malaysia, Indonesia, Vietnam, Cambodia, and Laos. With the wave of worldwide migration, it is entering the gene pool of diverse populations with greater consequences than expected. While HbE by itself presents as a mild anemia and a single gene for β-thalassemia is not serious, it remains unexplained why HbE/β-thalassemia (HbE/β-thal) is a grave disease with high morbidity and mortality. Patients often exhibit defective physical development, severe chronic anemia, and often die of cardiovascular disease and severe infections. Recent Advances: This article presents an overview of HbE/β-thal disease with an emphasis on new findings pointing to pathophysiological mechanisms derived from and initiated by the dysfunctional property of HbE as a reduced nitrite reductase concomitant with excess α-chains exacerbating unstable HbE, leading to a combination of nitric oxide imbalance, oxidative stress, and proinflammatory events. Additionally, we present new therapeutic strategies that are based on the emerging molecular-level understanding of the pathophysiology of this and other hemoglobinopathies. These strategies are designed to short-circuit the inflammatory cascade leading to devastating chronic morbidity and fatal consequences. Antioxid. Redox Signal. 26, 794-813.

  19. HbE/β-Thalassemia and Oxidative Stress: The Key to Pathophysiological Mechanisms and Novel Therapeutics

    Science.gov (United States)

    Sibmooh, Nathawut; Fucharoen, Suthat

    2017-01-01

    Abstract Significance: Oxidative stress and generation of free radicals are fundamental in initiating pathophysiological mechanisms leading to an inflammatory cascade resulting in high rates of morbidity and death from many inherited point mutation-derived hemoglobinopathies. Hemoglobin (Hb)E is the most common point mutation worldwide. The βE-globin gene is found in greatest frequency in Southeast Asia, including Thailand, Malaysia, Indonesia, Vietnam, Cambodia, and Laos. With the wave of worldwide migration, it is entering the gene pool of diverse populations with greater consequences than expected. Critical Issues: While HbE by itself presents as a mild anemia and a single gene for β-thalassemia is not serious, it remains unexplained why HbE/β-thalassemia (HbE/β-thal) is a grave disease with high morbidity and mortality. Patients often exhibit defective physical development, severe chronic anemia, and often die of cardiovascular disease and severe infections. Recent Advances: This article presents an overview of HbE/β-thal disease with an emphasis on new findings pointing to pathophysiological mechanisms derived from and initiated by the dysfunctional property of HbE as a reduced nitrite reductase concomitant with excess α-chains exacerbating unstable HbE, leading to a combination of nitric oxide imbalance, oxidative stress, and proinflammatory events. Future Directions: Additionally, we present new therapeutic strategies that are based on the emerging molecular-level understanding of the pathophysiology of this and other hemoglobinopathies. These strategies are designed to short-circuit the inflammatory cascade leading to devastating chronic morbidity and fatal consequences. Antioxid. Redox Signal. 26, 794–813. PMID:27650096

  20. CELLULAR DISTRIBUTION STUDIES OF THE NITRIC OXIDE-GENERATING ANTINEOPLASTIC PRODRUG JS-K, FORMULATED IN PLURONIC P123 MICELLES

    Science.gov (United States)

    Kaur, Imit; Terrazas, Moises; Kosak, Ken M.; Kern, Steven E.; Boucher, Kenneth M.; Shami, Paul J.

    2014-01-01

    Objective Nitric oxide (NO) possesses anti-tumor activity. It induces differentiation and apoptosis in acute myeloid leukemia (AML) cells. The NO prodrug O2-(2,4-dinitrophenyl)1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate, or JS-K, has potent antileukemic activity. JS-K is also active in vitro and in vivo against multiple myeloma, prostate cancer, non-small cell lung cancer, glioma and liver cancer. Using the Pluronic® P123 polymer, we have developed a micelle formulation for JS-K in order to increase its solubility and stability. The goal of the current study was to investigate the cellular distribution of JS-K in AML cells. Methods We investigated the intracellular distribution of JS-K (free drug) and JS-K formulated in P123 micelles (P123/JS-K) using HL-60 AML cells. We also studied the S-glutathionylating effects of JS-K on proteins in the cytoplasmic and nuclear cellular fractions. Key findings Both free JS-K and P123/JS-K accumulate primarily in the nucleus. Both free JS-K and P123/JS-K induced S-glutathionylation of nuclear proteins, although the effect produced was more pronounced with P123/JS-K. Minimal S-glutathionylation of cytoplasmic proteins was observed. Conclusions We conclude that a micelle formulation of JS-K increases its accumulation in the nucleus. Post-translational protein modification through S-glutathionylation may contribute to JS-K’s anti-leukemic properties. PMID:23927471

  1. Indium--tin oxide films radio frequency sputtered from specially formulated high density indium--tin oxide targets

    International Nuclear Information System (INIS)

    Kulkarni, S.; Bayard, M.

    1991-01-01

    High density ITO (indium--tin oxide) targets doped with Al 2 O 3 and SiO 2 manufactured in the Tektronix Ceramics Division have been used to rf sputter ITO films of various thicknesses on borosilicate glass substrates. Sputtering in an oxygen--argon gas mixture and annealing in forming gas, resulted in ITO films exhibiting 90% transmission at 550 nm and a sheet resistance of 15 Ω/sq for a thickness of 1100 A. Sputtering in an oxygen--argon gas mixture and annealing in air increased sheet resistance without a large effect on the transmission. Films sputtered in argon gas alone were transparent in the visible and the sheet resistance was found to be 100--180 Ω/sq for the same thickness, without annealing

  2. Magnetic and in vitro heating properties of implants formed in situ from injectable formulations and containing superparamagnetic iron oxide nanoparticles (SPIONs) embedded in silica microparticles for magnetically induced local hyperthermia

    International Nuclear Information System (INIS)

    Le Renard, Pol-Edern; Lortz, Rolf; Senatore, Carmine; Rapin, Jean-Philippe; Buchegger, Franz; Petri-Fink, Alke; Hofmann, Heinrich; Doelker, Eric; Jordan, Olivier

    2011-01-01

    The biological and therapeutic responses to hyperthermia, when it is envisaged as an anti-tumor treatment modality, are complex and variable. Heat delivery plays a critical role and is counteracted by more or less efficient body cooling, which is largely mediated by blood flow. In the case of magnetically mediated modality, the delivery of the magnetic particles, most often superparamagnetic iron oxide nanoparticles (SPIONs), is also critically involved. We focus here on the magnetic characterization of two injectable formulations able to gel in situ and entrap silica microparticles embedding SPIONs. These formulations have previously shown suitable syringeability and intratumoral distribution in vivo. The first formulation is based on alginate, and the second on a poly(ethylene-co-vinyl alcohol) (EVAL). Here we investigated the magnetic properties and heating capacities in an alternating magnetic field (141 kHz, 12 mT) for implants with increasing concentrations of magnetic microparticles. We found that the magnetic properties of the magnetic microparticles were preserved using the formulation and in the wet implant at 37 o C, as in vivo. Using two orthogonal methods, a common SLP (20 W g -1 ) was found after weighting by magnetic microparticle fraction, suggesting that both formulations are able to properly carry the magnetic microparticles in situ while preserving their magnetic properties and heating capacities. - Research highlights: → Magnetic formulations that form implants on injection into tissues are proposed for hyperthermia. → Superparamagnetic properties of the SPION-silica composite microparticles are preserved in the wet implants. → Heat-dissipating properties (SLP of 20 W/g of implant) support in vivo use.

  3. A comparative evaluation of a dipicolinic acid based dilute chemical decontaminant formulation with respect to its efficacy for dissolution of iron oxides

    Energy Technology Data Exchange (ETDEWEB)

    Kamal Kishore; Dey, G.R.; Naik, D.B.; Moorthy, P.N. [Applied Chemistry Division, Bhabha Atomic Research Centre, Mumbai-400 085 (India)

    1998-12-31

    A dilute chemical decontamination formulation containing dipicolinic acid (2,6-pyridine dicarboxylic acid PDCA) and ascorbic acid (AA) has been found to be effective in dissolving magnetite, nickel ferrite and haemetite. Its main advantages arise because of (i) good solubility of the two constituents (ii) lack of absorption on the cation exchanger from acidic media during regenerative decontamination process (iii) stability to ionizing radiation and (iv) low corrosion rate for carbon steel. Dissolution rates of iron oxides in this formulation are as good as or better than in other well known formulations. (author)

  4. Nitric oxide, a double edged sword in cancer biology: searching for therapeutic opportunities.

    Science.gov (United States)

    Mocellin, Simone; Bronte, Vincenzo; Nitti, Donato

    2007-05-01

    Nitric oxide (NO) is a pleiotropic molecule critical to a number of physiological and pathological processes. The last decade has witnessed major advances in dissecting NO biology and its role in cancer pathogenesis. However, the complexity of the interactions between different levels of NO and several aspects of tumor development/progression has led to apparently conflicting findings. Furthermore, both anti-NO and NO-based anticancer strategies appear effective in several preclinical models. This paradoxical dichotomy is leaving investigators with a double challenge: to determine the net impact of NO on cancer behavior and to define the therapeutic role of NO-centered anticancer strategies. Only a comprehensive and dynamic view of the cascade of molecular and cellular events underlying tumor biology and affected by NO will allow investigators to exploit the potential antitumor properties of drugs interfering with NO metabolism. Available data suggest that NO should be considered neither a universal target nor a magic bullet, but rather a signal transducer to be modulated according to the molecular makeup of each individual cancer and the interplay with conventional antineoplastic agents. (c) 2006 Wiley Periodicals, Inc.

  5. Nitric oxide nanoparticles: pre-clinical utility as a therapeutic for intramuscular abscesses.

    Science.gov (United States)

    Schairer, David; Martinez, Luis R; Blecher, Karin; Chouake, Jason; Nacharaju, Parimala; Gialanella, Philip; Friedman, Joel M; Nosanchuk, Joshua D; Friedman, Adam

    2012-01-01

    Nitric oxide (NO) is a critical component of host defense against invading pathogens; however, its therapeutic utility is limited due to a lack of practical delivery systems. Recently, a NO-releasing nanoparticulate platform (NO-np) was shown to have in vitro broad-spectrum antimicrobial activity and in vivo pre-clinical efficacy in a dermal abscess model. To extend these findings, both topical (TP) and intralesional (IL) NO-np administration was evaluated in a MRSA intramuscular murine abscess model and compared with vancomycin. All treatment arms accelerated abscess clearance clinically, histologically, and by microbiological assays on both days 4 and 7 following infection. However, abscesses treated with NO-np via either route demonstrated a more substantial, statistically significant decrease in bacterial survival based on colony forming unit assays and histologically revealed less inflammatory cell infiltration and preserved muscular architecture. These data suggest that the NO-np may be an effective addition to our armament for deep soft tissue infections.

  6. The effect of Cissus quadrangularis (CQR-300 and a Cissus formulation (CORE on obesity and obesity-induced oxidative stress

    Directory of Open Access Journals (Sweden)

    Agbor Gabriel A

    2007-02-01

    Full Text Available Abstract Aim Obesity is generally linked to complications in lipid metabolism and oxidative stress. The aim of this study was to compare the effect of a proprietary extract of Cissus quadrangularis (CQR-300 to that of a proprietary formulation containing CQR-300 (CORE on weight, blood lipids, and oxidative stress in overweight and obese people. Methods The first part of the study investigated the in vitro antioxidant properties of CQR-300 and CORE using 3 different methods, while the second part of the study was a double-blind placebo controlled design, involving initially 168 overweight and obese persons (38.7% males; 61.3% females; ages 19–54, of whom 153 completed the study. All participants received two daily doses of CQR-300, CORE, or placebo and were encouraged to maintain their normal levels of physical activity. Anthropometric measurements and blood sampling were done at the beginning and end of the study period. Results CQR-300 as well as CORE exhibited antioxidant properties in vitro. They also acted as in vivo antioxidants, bringing about significant (p Conclusion CQR-300 (300 mg daily and CORE (1028 mg daily brought about significant reductions in weight and blood glucose levels, while decreasing serum lipids thus improving cardiovascular risk factors. The increase in plasma 5-HT and creatinine for both groups hypothesizes a mechanism of controlling appetite and promoting the increase of lean muscle mass by Cissus quadrangularis, thereby supporting the clinical data for weight loss and improving cardiovascular health.

  7. Antimicrobial and antioxidant potentials of biosynthesized colloidal zinc oxide nanoparticles for a fortified cold cream formulation: A potent nanocosmeceutical application.

    Science.gov (United States)

    S, Sonia; H, Linda Jeeva Kumari; K, Ruckmani; M, Sivakumar

    2017-10-01

    Nanocosmeceuticals are promising applications of nanotechnology in personal care industries. Zinc oxide is an inorganic material that is non-toxic and skin compatible with self-cleansing and microbicidal properties. Herein, exploitation of colloidal zinc oxide nanoparticles (ZnONps) as potent biomaterial for a topical formulation of cosmetic and dermatological significance is employed. ZnONps were green synthesized using environmentally benign Adhatoda vasica leaf extract and characterized by UV-Vis absorption spectroscopy, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), dynamic light scattering (DLS), high-resolution transmission electron microscopy (HR-TEM) and energy-dispersive X-ray spectroscopy (EDX). The results reveal that the biosynthesized ZnONps exhibit an absorption peak at 352nm. XRD and HR-TEM analyses confirm the hexagonal wurtzite structure of ZnONps with particle size of about 10nm to 12nm. Elemental analysis by EDX confirms the presence of zinc and oxygen. Zeta potential of -24.6mV affirms the stability of nanoparticles. The antibacterial and antifungal activities of biosynthesized ZnONps exhibit mean zone of inhibition from 08.667±0.282 to 21.666±0.447 (mm) and 09.000±0.177 to 19.000±0.307 (mm) respectively, in a dose-dependent manner. The IC 50 value exerted from the antioxidant activity of ZnONps is found to be 139.27μgmL -1 . ZnONps infused cold cream formulation of microbicidal and antioxidant properties was further tested against clinical skin pathogens. The nano-based cold cream exhibited significant inhibitory action against Candida sp., which showed resistance against a commercial antifungal cream (2%). Therefore, this study demonstrates the exploitation of ZnONps as promising colloidal drug carriers in cosmeceuticals that can significantly alleviate human skin infections and oxidative stress induced cellular damage. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. EFFECT OF A PLURONIC® P123 FORMULATION ON THE NITRIC OXIDE-GENERATING DRUG JS-K

    Science.gov (United States)

    Kaur, Imit; Kosak, Ken M.; Terrazas, Moises; Herron, James N.; Kern, Steven E.; Boucher, Kenneth M.; Shami, Paul J.

    2014-01-01

    Purpose O2-(2,4-dinitrophenyl)1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate] or JS-K is a nitric oxide-producing prodrug of the arylated diazeniumdiolate class with promising anti-tumor activity. JS-K has challenging solubility and stability properties. We aimed to characterize and compare Pluronic® P123-formulated JS-K (P123/JS-K) with free JS-K. Methods We determined micelle size, shape, and critical micelle concentration of Pluronic® P123. Efficacy was evaluated in vitro using HL-60 and U937 cells and in vivo in a xenog raft in NOD/SCID IL2Rγnull mice using HL-60 cells. We compared JS-K and P123/JS-K stability in different media. We also compared plasma protein binding of JS-K and P123/JS-K. We determined the binding and Stern Volmer constants, and thermodynamic parameters. Results Spherical P123/JS-K micelles were smaller than blank P123. P123/JS-K formulation was more stable in buffered saline, whole blood, plasma and RPMI media as compared to free JS-K. P123 affected the protein binding properties of JS-K. In vitro it was as efficacious as JS-K alone when tested in HL-60 and U937 cells and in vivo greater tumor regression was observed for P123/JS-K treated NOD/SCID IL2Rγnull mice when compared to free JS-K-treated NOD/SCID IL2Rγnull mice. Conclusions Pluronic® P123 solubilizes, stabilizes and affects the protein binding characteristics of JS-K. P123/JS-K showed more in vivo anti-tumor activity than free JS-K. PMID:25330743

  9. Effect of a Pluronic(®) P123 formulation on the nitric oxide-generating drug JS-K.

    Science.gov (United States)

    Kaur, Imit; Kosak, Ken M; Terrazas, Moises; Herron, James N; Kern, Steven E; Boucher, Kenneth M; Shami, Paul J

    2015-04-01

    O(2)-(2,4-dinitrophenyl)1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate] or JS-K is a nitric oxide-producing prodrug of the arylated diazeniumdiolate class with promising anti-tumor activity. JS-K has challenging solubility and stability properties. We aimed to characterize and compare Pluronic(®) P123-formulated JS-K (P123/JS-K) with free JS-K. We determined micelle size, shape, and critical micelle concentration of Pluronic(®) P123. Efficacy was evaluated in vitro using HL-60 and U937 cells and in vivo in a xenograft in NOD/SCID IL2Rγ (null) mice using HL-60 cells. We compared JS-K and P123/JS-K stability in different media. We also compared plasma protein binding of JS-K and P123/JS-K. We determined the binding and Stern Volmer constants, and thermodynamic parameters. Spherical P123/JS-K micelles were smaller than blank P123. P123/JS-K formulation was more stable in buffered saline, whole blood, plasma and RPMI media as compared to free JS-K. P123 affected the protein binding properties of JS-K. In vitro it was as efficacious as JS-K alone when tested in HL-60 and U937 cells and in vivo greater tumor regression was observed for P123/JS-K treated NOD/SCID IL2Rγ (null) mice when compared to free JS-K-treated NOD/SCID IL2Rγ (null) mice. Pluronic(®) P123 solubilizes, stabilizes and affects the protein binding characteristics of JS-K. P123/JS-K showed more in vivo anti-tumor activity than free JS-K.

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

    Directory of Open Access Journals (Sweden)

    Motta Bruna

    2012-05-01

    Full Text Available Abstract Background Over the last few decades, canine and feline thelaziosis caused by Thelazia callipaeda eye worms has gained the attention of the veterinary community due to the spread of this ocular infestation in geographical areas previously regarded as non endemic. The therapeutic efficacy of milbemycin oxime/praziquantel tablets (Milbemax® against T. callipaeda was tested in naturally infested dogs and cats. Methods From January 2009 to July 2011 a placebo controlled and randomized field study was conducted in T. callipaeda endemic areas of Switzerland (CH and Italy (ITA involving client-owned animals. Dogs (n = 56 and cats (n = 31 were physically examined at enrolment Day 0 (D0 and twice afterwards (D7 and D14. Infested animals were orally treated with Milbemax® or with placebo tablets on D0 and, if an animal was found still infested with T. callipaeda, also on D7. On D14 nematodes were flushed from the conjunctiva, identified and counted. Results Out of 56 dogs, 43 were included in the statistical analysis, whereas 13 were excluded because the products under investigation were not administered with food, as required by the label. On D7 and D14, 72.7% and 90.9% of treated dogs were eye worm free, whereas in the placebo group 95.2% and 76.2% still harbored nematodes, resulting in a mean percentage worm count reduction for the Milbemax® group of 86.1% and 96.8%, respectively. Both results were significantly higher (p = 0.0001 than the placebo group. Out of the 31 cats included in the study at D7 and D14, 53.3% and 73.3% treated with Milbemax® were free of T. callipaeda, while 81.3% and 73.3 in the placebo group were still harbouring eye worms, resulting in a mean percentage worm count reduction for the treated group of 62.2% and 80.0%, respectively. Both results were significantly higher (p = 0.0106 and p = 0.0043 than the placebo group. Conclusions The commercial formulation of milbemycin oxime at the minimal dose

  11. Paraquat induces oxidative stress, neuronal loss in substantia nigra region and Parkinsonism in adult rats: Neuroprotection and amelioration of symptoms by water-soluble formulation of Coenzyme Q10

    Directory of Open Access Journals (Sweden)

    Sridhar TS

    2009-07-01

    Full Text Available Abstract Background Parkinson's disease, for which currently there is no cure, develops as a result of progressive loss of dopamine neurons in the brain; thus, identification of any potential therapeutic intervention for disease management is of a great importance. Results Here we report that prophylactic application of water-soluble formulation of coenzyme Q10 could effectively offset the effects of environmental neurotoxin paraquat, believed to be a contributing factor in the development of familial PD. In this study we utilized a model of paraquat-induced dopaminergic neurodegeneration in adult rats that received three weekly intra-peritoneal injections of the herbicide paraquat. Histological and biochemical analyses of rat brains revealed increased levels of oxidative stress markers and a loss of approximately 65% of dopamine neurons in the substantia nigra region. The paraquat-exposed rats also displayed impaired balancing skills on a slowly rotating drum (rotorod evidenced by their reduced spontaneity in gait performance. In contrast, paraquat exposed rats receiving a water-soluble formulation of coenzyme Q10 in their drinking water prior to and during the paraquat treatment neither developed neurodegeneration nor reduced rotorod performance and were indistinguishable from the control paraquat-untreated rats. Conclusion Our data confirmed that paraquat-induced neurotoxicity represents a convenient rat model of Parkinsonian neurodegeneration suitable for mechanistic and neuroprotective studies. This is the first preclinical evaluation of a water-soluble coenzyme Q10 formulation showing the evidence of prophylactic neuroprotection at clinically relevant doses.

  12. Heterocyclic N-Oxides – An Emerging Class of Therapeutic Agents

    Science.gov (United States)

    Mfuh, Adelphe M.; Larionov, Oleg V.

    2016-01-01

    Heterocyclic N-oxides have emerged as potent compounds with anticancer, antibacterial, antihypertensive, antiparasitic, anti-HIV, anti-inflammatory, herbicidal, neuroprotective, and procognitive activities. The N-oxide motif has been successfully employed in a number of recent drug development projects. This review surveys the emergence of this scaffold in the mainstream medicinal chemistry with a focus on the discovery of the heterocyclic N-oxide drugs, N-oxide-specific mechanisms of action, drug-receptor interactions and synthetic avenues to these compounds. As the first review on this subject that covers the developments since 1950s to date, it is expected that it will inspire wider implementation of the heterocyclic N-oxide motif in the rational design of new medicinal agents. PMID:26087764

  13. 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

  14. Oxidative stress biomarkers in different tissues of rainbow trout (Oncorhynchus mykiss exposed to Disinfectant-CIP formulated with peracetic acid and hydrogen peroxide

    Directory of Open Access Journals (Sweden)

    Tkachenko Halyna

    2014-09-01

    Full Text Available The aim of study was to determine the effects of exposure to the product DEZYNFEKTANT-CIP (Eng. - Disinfectant-CIP, which is formulated with peracetic acid and hydrogen peroxide, on oxidative stress biomarkers (lipid peroxidation (LPO levels and the carbonyl content of oxidatively modified proteins and antioxidant defenses (superoxide dismutase (SOD, catalase (CAT, glutathione reductase (GR, glutathione peroxidase (GPx, total antioxidant capacity in muscle, gill, hepatic, and cardiac tissues of rainbow trout, Oncorhynchus mykiss (Walbaum. LPO and carbonyl contents changed with tissue type. Exposure to Disinfectant-CIP led to a significant decrease in LPO in muscle tissues and carbonyl content in muscle and gill tissues. The inhibition of SOD and CAT activity in muscle, hepatic, and cardiac tissues was observed probably because of increased oxidative stress during disinfection; however, hepatic and cardiac GPx activity increased in an attempt to counteract oxidative stress. We suggest that oxidative stress during the oxidation of peracetic acid and hydrogen peroxide could be counteracted by the antioxidant system in trout tissues. Correlative analysis between oxidative stress biomarkers and antioxidant defense confirms the pivotal role of SOD and CAT against CIP-induced oxidative stress

  15. The influence of polymeric excipients on the process of pharmaceutical availability of therapeutic agents from a model drug form. Part I. In formulations with controlled disintegration and release time.

    Science.gov (United States)

    Nachajski, Michal Jakub; Zgoda, Marian Mikołaj

    2010-01-01

    Pre-formulation research was conducted on the application of Ex. Echinaceae aq. siccum in the production of a quickly disintegrating suspension tablet, a lozenge with kariostatic sugar alcohols (mannitol, sorbitol), and, above all, a solid drug form with controlled release of therapeutic agents included in the extract. Morphological parameters of tablets obtained in the course of experiment were estimated and the profiles of the release (diffusion) ofhydrophilic therapeutic agents into model receptor fluids with varying values of osmolarity (0.1 mol HCl approximately 200 mOsm/l, hypotonic hydrating fluid approximately 143 mOsm/l, and compensatory paediatric fluid approximately 272 mOsm/l) were examined. The study focused on the technological problem of determining the effect of hydrogel Carbopol structure on the ordering of diffusion ofhydrophilic therapeutic agents from a model drug form (a tablet) into model fluids with variable osmolarity.

  16. Calcium-activated potassium channels - a therapeutic target for modulating nitric oxide in cardiovascular disease?

    DEFF Research Database (Denmark)

    Dalsgaard, Thomas; Kroigaard, Christel; Simonsen, Ulf

    2010-01-01

    IMPORTANCE OF THE FIELD: Cardiovascular risk factors are often associated with endothelial dysfunction, which is also prognostic for occurrence of cardiovascular events. Endothelial dysfunction is reflected by blunted vasodilatation and reduced nitric oxide (NO) bioavailability. Endothelium...

  17. New Pathogenic Concepts and Therapeutic Approaches to Oxidative Stress in Chronic Kidney Disease

    DEFF Research Database (Denmark)

    Pedraza-Chaverri, José; Sánchez-Lozada, Laura G; Osorio-Alonso, Horacio

    2016-01-01

    In chronic kidney disease inflammatory processes and stimulation of immune cells result in overproduction of free radicals. In combination with a reduced antioxidant capacity this causes oxidative stress. This review focuses on current pathogenic concepts of oxidative stress for the decline...... and pharmacologic therapies for hyperuricemia are discussed. Finally, we review some new therapy options in diabetic nephropathy including antidiabetic agents (noninsulin dependent), plant antioxidants, and food components as alternative antioxidant therapies....

  18. Screening of traditional Chinese medicines with therapeutic potential on chronic obstructive pulmonary disease through inhibiting oxidative stress and inflammatory response.

    Science.gov (United States)

    Zhou, Ming-Xing; Wei, Xuan; Li, Ai-Ling; Wang, Ai-Min; Lu, Ling-Zi; Yang, Yue; Ren, Dong-Mei; Wang, Xiao-Ning; Wen, Xue-Sen; Lou, Hong-Xiang; Shen, Tao

    2016-09-13

    Chronic obstructive pulmonary disease (COPD) is a major public health problem and gives arise to severe chronic morbidity and mortality in the world. Inflammatory response and oxidative stress play dominant roles in the pathological mechanism of COPD, and have been regarded to be two important targets for the COPD therapy. Traditional Chinese medicines (TCMs) possess satisfying curative effects on COPD under guidance of the TCM theory in China, and merit in-depth investigations as a resource of lead compounds. One hundred ninety-six of TCMs were collected, and extracted to establish a TCM extract library, and then further evaluated for their potency on inhibitions of oxidative stress and inflammatory response using NADP(H):quinone oxidoreductase (QR) assay and nitric oxide (NO) production assay, respectively. Our investigation observed that 38 of the tested TCM extracts induced QR activity in hepa 1c1c7 murine hepatoma cells, and 55 of them inhibited NO production in RAW 264.7 murine macrophages at the tested concentrations. Noteworthily, 20 of TCM extracts simultaneously inhibited oxidative stress and inflammatory responses. The observed bioactive TCMs, particularly these 20 TCMs with dual inhibitory effects, might be useful for the treatment of COPD. More importantly, the results of the present research afford us an opportunity to discover new lead molecules as COPD therapeutic agents from these active TCMs.

  19. Evaluation of a commercially available molybdate formulation and zinc oxide boluses in preventing hepatic copper accumulation and thus enzootic icterus in sheep

    Directory of Open Access Journals (Sweden)

    C.J. Botha

    2001-07-01

    Full Text Available The efficacy of a molybdate formulation and a zinc oxide bolus as prophylactic agents for enzootic icterus was evaluated in sheep. Before copper loading, liver biopsies were performed on 12 male, 6-month-old, Mutton Merino sheep to determine hepatic copper (Cu and zinc (Zn concentrations. The animals were restrictively randomised according to liver copper concentrations to 3 treatment groups (n = 4 to achieve similar mean liver copper concentrations per group. All sheep received 4 m /kg of a 0.5 %aqueous solution of CuSO4·5H2O intraruminally 7 days per week for 10 weeks. On Day 0 the sheep in the Mo-group were injected subcutaneously with 42 mg molybdenum (Mo contained in a commercial molybdate formulation. The animals in the Zn-group each received a zinc oxide bolus, containing 43 g zinc oxide, via a rumen cannula. Treatment was repeated on Day 42. Four animals served as untreated controls. Urinary copper excretion, plasma copper concentration, haematocrit and glutamate dehydrogenase (GLDH activity were determined throughout the trial. The animals were sacrificed after 10 weeks and liver samples were submitted for histopathological examination. Liver and kidney copper and zinc concentrations were determined. Neither the molybdate treatment nor the zinc oxide boluses prevented hepatic copper accumulation. The urinary copper excretion, plasma copper concentration, haematocrit and GLDH activity were not significantly different (P > 0.05 from the controls.

  20. Obesity, Oxidative Stress, Adipose Tissue Dysfunction, and the Associated Health Risks: Causes and Therapeutic Strategies

    Science.gov (United States)

    Manna, Prasenjit

    2015-01-01

    Abstract Obesity is gaining acceptance as a serious primary health burden that impairs the quality of life because of its associated complications, including diabetes, cardiovascular diseases, cancer, asthma, sleep disorders, hepatic dysfunction, renal dysfunction, and infertility. It is a complex metabolic disorder with a multifactorial origin. Growing evidence suggests that oxidative stress plays a role as the critical factor linking obesity with its associated complications. Obesity per se can induce systemic oxidative stress through various biochemical mechanisms, such as superoxide generation from NADPH oxidases, oxidative phosphorylation, glyceraldehyde auto-oxidation, protein kinase C activation, and polyol and hexosamine pathways. Other factors that also contribute to oxidative stress in obesity include hyperleptinemia, low antioxidant defense, chronic inflammation, and postprandial reactive oxygen species generation. In addition, recent studies suggest that adipose tissue plays a critical role in regulating the pathophysiological mechanisms of obesity and its related co-morbidities. To establish an adequate platform for the prevention of obesity and its associated health risks, understanding the factors that contribute to the cause of obesity is necessary. The most current list of obesity determinants includes genetic factors, dietary intake, physical activity, environmental and socioeconomic factors, eating disorders, and societal influences. On the basis of the currently identified predominant determinants of obesity, a broad range of strategies have been recommended to reduce the prevalence of obesity, such as regular physical activity, ad libitum food intake limiting to certain micronutrients, increased dietary intake of fruits and vegetables, and meal replacements. This review aims to highlight recent findings regarding the role of oxidative stress in the pathogenesis of obesity and its associated risk factors, the role of dysfunctional adipose tissue

  1. Obesity, Oxidative Stress, Adipose Tissue Dysfunction, and the Associated Health Risks: Causes and Therapeutic Strategies.

    Science.gov (United States)

    Manna, Prasenjit; Jain, Sushil K

    2015-12-01

    Obesity is gaining acceptance as a serious primary health burden that impairs the quality of life because of its associated complications, including diabetes, cardiovascular diseases, cancer, asthma, sleep disorders, hepatic dysfunction, renal dysfunction, and infertility. It is a complex metabolic disorder with a multifactorial origin. Growing evidence suggests that oxidative stress plays a role as the critical factor linking obesity with its associated complications. Obesity per se can induce systemic oxidative stress through various biochemical mechanisms, such as superoxide generation from NADPH oxidases, oxidative phosphorylation, glyceraldehyde auto-oxidation, protein kinase C activation, and polyol and hexosamine pathways. Other factors that also contribute to oxidative stress in obesity include hyperleptinemia, low antioxidant defense, chronic inflammation, and postprandial reactive oxygen species generation. In addition, recent studies suggest that adipose tissue plays a critical role in regulating the pathophysiological mechanisms of obesity and its related co-morbidities. To establish an adequate platform for the prevention of obesity and its associated health risks, understanding the factors that contribute to the cause of obesity is necessary. The most current list of obesity determinants includes genetic factors, dietary intake, physical activity, environmental and socioeconomic factors, eating disorders, and societal influences. On the basis of the currently identified predominant determinants of obesity, a broad range of strategies have been recommended to reduce the prevalence of obesity, such as regular physical activity, ad libitum food intake limiting to certain micronutrients, increased dietary intake of fruits and vegetables, and meal replacements. This review aims to highlight recent findings regarding the role of oxidative stress in the pathogenesis of obesity and its associated risk factors, the role of dysfunctional adipose tissue in

  2. Therapeutic potentials of Houttuynia cordata Thunb. against inflammation and oxidative stress: A review.

    Science.gov (United States)

    Shingnaisui, Khanchuila; Dey, Tapan; Manna, Prasenjit; Kalita, Jatin

    2018-06-28

    Houttuynia cordata Thunb. (Family: Saururaceae) is an herbaceous perennial plant that grows in moist and shady places. The plant is well known among the people of diverse cultures across Japan, Korea, China and North-East India for its medicinal properties. Traditionally the plant is used for its various beneficial properties against inflammation, pneumonia, severe acute respiratory syndrome, muscular sprain, stomach ulcer etc. Oxidative stress and inflammation were found to be linked with most of the diseases in recent times. Many ancient texts from Chinese Traditional Medicine, Ayurveda and Siddha, and Japanese Traditional medicine have documented the efficacy of H. cordata against oxidative stress and inflammation. This review aims to provide up-to-date and comprehensive information on the efficacy of H. cordata extracts as well as its bioactive compounds both in vitro and in vivo, against oxidative stress and inflammation MATERIALS AND METHODS: Relevant information on H. cordata against oxidative stress and inflammation were collected from the established scientific databases such as NCBI, Web of Science, ScienceDirect, Elsevier, and Springer. Additionally, a few books and magazines were also consulted to get the important information. Herbal medicines or plant products were traditionally being used for treating the oxidative stress and inflammation related diseases in diverse communities across the world. Scientifically, H. cordata has shown to target several signaling pathways and found to effectively reduce the oxidative stress and inflammation. Phyto-constituents such as afzelin, hyperoside and quercitrin have shown to reduce inflammation both in vitro and in vivo models. These molecules were also shown to have strong antioxidant properties both in vivo and in vitro models. H. cordata extracts and its bioactive molecules were shown to have both anti-inflammatory and anti-oxidative properties. As both in vitro and in vivo studies were shown that H. cordata

  3. Low-fat frankfurters formulated with a healthier lipid combination as functional ingredient: microstructure, lipid oxidation, nitrite content, microbiological changes and biogenic amine formation.

    Science.gov (United States)

    Delgado-Pando, Gonzalo; Cofrades, Susana; Ruiz-Capillas, Claudia; Solas, Maria Teresa; Triki, Mehdi; Jiménez-Colmenero, Francisco

    2011-09-01

    Oil (healthier lipid combination of olive, linseed and fish oils)-in-water emulsions stabilized with different protein systems (prepared with sodium caseinate (SC), soy protein isolate (SPI), and microbial transglutaminase (MTG)) were used as pork backfat replacers in low-fat frankfurters. Microstructure, lipid oxidation, nitrite content, microbiological changes and biogenic amine formation of frankfurters were analyzed and found to be affected by the type of oil-in-water emulsion and by chilling storage (2° C, 41 days). Although the lipid oxidation levels attained were low, replacement of animal fat by healthier oil combinations in frankfurter formulation did promote a slight increase in lipid oxidation. Residual nitrite was affected (P nitrite was detectable in the product after processing and 17-46% at the end of storage. The microbial population was low in all formulations during chilling storage. Spermine was the most abundant amine (19-20 mg/kg), but similar in level to all samples. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Integrative medical therapy: examination of meditation's therapeutic and global medicinal outcomes via nitric oxide (review).

    Science.gov (United States)

    Stefano, George B; Esch, Tobias

    2005-10-01

    Relaxation techniques are part of the integrative medicine movement that is of growing importance for mainstream medicine. Complementary medical therapies have the potential to affect many physiological systems. Repeatedly studies show the benefits of the placebo response and relaxation techniques in the treatment of hypertension, cardiac arrhythmias, chronic pain, insomnia, anxiety and mild and moderate depression, premenstrual syndrome, and infertility. In itself, relaxation is characterized by a decreased metabolism, heart rate, blood pressure, and rate of breathing as well as an increase in skin temperature. Relaxation approaches, such as progressive muscle relaxation, autogenic training, meditation and biofeedback, are effective in lowering systolic and diastolic blood pressure in hypertensive patients by a significant margin. Given this association with changes in vascular tone, we have hypothesized that nitric oxide, a demonstrated vasodilator substance, contribute to physiological activity of relaxation approaches. We examined the scientific literature concerning the disorders noted earlier for their nitric oxide involvement in an attempt to provide a molecular rationale for the positive effects of relaxation approaches, which are physiological and cognitive process. We conclude that constitutive nitric oxide may crucially contribute to potentially beneficial outcomes and effects in diverse pathologies, exerting a global healing effect.

  5. Towards boron neutron capture therapy: the formulation and preliminary in vitro evaluation of liposomal vehicles for the therapeutic delivery of the dequalinium salt of bis-nido-carborane.

    Science.gov (United States)

    Theodoropoulos, Dimitrios; Rova, Aikaterini; Smith, James R; Barbu, Eugen; Calabrese, Gianpiero; Vizirianakis, Ioannis S; Tsibouklis, John; Fatouros, Dimitrios G

    2013-11-15

    Liposomes of phosphatidylcholine or of dimyristoylphosphatidylcholine that incorporate bis-nido-carborane dequalinium salt are stable in physiologically relevant media and have in vitro toxicity profiles that appear to be compatible with potential therapeutic applications. These features render the structures suitable candidate boron-delivery vehicles for evaluation in the boron neutron capture therapy of cancer. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Endothelial dysfunction in metabolic diseases: role of oxidation and possible therapeutic employment of N-acetylcysteine.

    Science.gov (United States)

    Masha, A; Martina, V

    2014-01-01

    Several metabolic diseases present a high cardiovascular mortality due to endothelial dysfunction consequences. In the last years of the past century, it has come to light that the endothelial cells, previously considered as inert in what regards an eventual secretion activity, play a pivotal role in regulating different aspects of the vascular function (endothelial function). It was clearly demonstrated that the endothelium acts as a real active organ, owning endocrine, paracrine and autocrine modulation activities by means of which it is able to regulate the vascular homeostasis. The present review will investigate the relationship between some metabolic diseases and the endothelial dysfunction and in particular the mechanisms underlying the effects of metabolic pathologies on the endothelium. Furthermore, it will consider the possible therapeutic employment of the N-acetilcysteine in such conditions.

  7. Personalized disease-specific protein corona influences the therapeutic impact of graphene oxide

    Science.gov (United States)

    Hajipour, Mohammad Javad; Raheb, Jamshid; Akhavan, Omid; Arjmand, Sareh; Mashinchian, Omid; Rahman, Masoud; Abdolahad, Mohammad; Serpooshan, Vahid; Laurent, Sophie; Mahmoudi, Morteza

    2015-05-01

    The hard corona, the protein shell that is strongly attached to the surface of nano-objects in biological fluids, is recognized as the first layer that interacts with biological objects (e.g., cells and tissues). The decoration of the hard corona (i.e., the type, amount, and conformation of the attached proteins) can define the biological fate of the nanomaterial. Recent developments have revealed that corona decoration strongly depends on the type of disease in human patients from which the plasma is obtained as a protein source for corona formation (referred to as the `personalized protein corona'). In this study, we demonstrate that graphene oxide (GO) sheets can trigger different biological responses in the presence of coronas obtained from various types of diseases. GO sheets were incubated with plasma from human subjects with different diseases/conditions, including hypofibrinogenemia, blood cancer, thalassemia major, thalassemia minor, rheumatism, fauvism, hypercholesterolemia, diabetes, and pregnancy. Identical sheets coated with varying protein corona decorations exhibited significantly different cellular toxicity, apoptosis, and uptake, reactive oxygen species production, lipid peroxidation and nitrogen oxide levels. The results of this report will help researchers design efficient and safe, patient-specific nano biomaterials in a disease type-specific manner for clinical and biological applications.The hard corona, the protein shell that is strongly attached to the surface of nano-objects in biological fluids, is recognized as the first layer that interacts with biological objects (e.g., cells and tissues). The decoration of the hard corona (i.e., the type, amount, and conformation of the attached proteins) can define the biological fate of the nanomaterial. Recent developments have revealed that corona decoration strongly depends on the type of disease in human patients from which the plasma is obtained as a protein source for corona formation (referred

  8. Therapeutic iron : Evaluation of methods to assess intravenous iron safety profiles and the development of a novel formulation for oral iron delivery

    NARCIS (Netherlands)

    Span, K.|info:eu-repo/dai/nl/357800842

    2018-01-01

    Iron treatment is necessary to replenish iron deficit due to several clinical conditions such as chronic diseases. However, as an excess of iron can result in redox imbalance resulting in oxidative stress and thus severe damage to tissue and organs, it is of utmost importance to develop iron

  9. Green synthesized zinc oxide nanoparticles as a therapeutic tool to combat candidiasis

    Science.gov (United States)

    Rathod, Tejas; Padalia, Hemali; Chanda, Sumitra

    2017-05-01

    Advancement of modern medicine, the increasing ratio of immunocompromised and immunosuppressive individuals is increased in hospitalized with serious underlying disease. This has resulted in a rise in the incidence of fungal infections, especially those due to Candida species. For many years the conventional antibiotic therapy has been critical in the fight against Candidiasis. Candidiasis is a fungal infection due to various types of Candida (yeast) species. In this study, zinc oxide nanoparticles (ZnONPs) were synthesized using the Cinnamomum verum bark plus Cassia auriculata leaf powder extracts. The characterization of synthesized ZnONPs was done by UV-Vis spectrophotometer and SEM analysis. The average size of nanoparticles was 77 nm. Synergistic anticandidal activity of ZnONPs (ZnONPs plus antibiotics) was determined by disc diffusion method against 16 multidrug resistant clinical pathogens of Candida species. Antibiotic Ketoconazole plus ZnONPs showed best synergistic anticandidal activity against all the 16 isolates. Green synthesized ZnONPs appears to be a new promising approach to fight against Candidiasis.

  10. 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

    Science.gov (United States)

    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.

  11. A Very Simple and Sensitive Spectrofluorimetric Method Based on the Oxidation with Cerium (IV for the Determination of Four Different Drugs in Their Pharmaceutical Formulations

    Directory of Open Access Journals (Sweden)

    Ahad Bavili-Tabrizi, Farshad Bahrami, Hossein Badrouj

    2017-03-01

    Full Text Available Background: Methyldopa is a catecholamine widely used as an antihypertensive agent. Pioglitazone is an oral anti-hyperglycemic agent. It is used for the treatment of diabetes mellitus type 2. A survey of the literature reveals that only one spectrofluorimetric method has been reported for the determination of pioglitazone in pharmaceutical preparations. Atenolol and metoprolol are prescription drugs of the β-blocker class with hypotensive action to treat angina, MI, alcohol syndrome, hypertension, and arrhythmias. A survey of the literature reveals that several spectrofluorimetric methods have been reported for the determination of atenolol and metoprolol in pharmaceutical preparations. In continuing of our studies on the developing of simple and fast spectrofluorimetric methods for determination of drugs and active ingredients, in this work we have developed a spectrofluorimetric method based on the oxidation with cerium (IV for the determination of studied drugs in their pharmaceutical formulations. Methods: A simple, rapid and sensitive spectrofluorimetric method was developed for the determination of studied drugs in pharmaceutical formulations. Proposed method is based on the oxidation of these drugs with Ce (IV to produce Ce (III, and its fluorescence was monitored at 356 ± 3 nm after excitation at 254 ± 3 nm. Results: The variables affecting oxidation of each drug were studied and optimized. Under the experimental conditions used, the calibration graphs were linear over the range of 25-450, 50-550, 15-800 and 15-800 ng/mL in the case of atenolol, metoprolol, pioglitazone and methyldopa, respectively. The limit of detection was found to be 8.27, 16.5, 1.52 and 5.08 ng/mL in the case of atenolol, metoprolol, pioglitazone and methyldopa, respectively. Intra- and inter-day assay precisions, expressed as the relative standard deviation (RSD, were lower than 3% in all cases. Conclusion: The proposed method was applied to the determination of

  12. A novel nitric oxide-based anticancer therapeutics by macrophage-targeted poly(l-arginine)-based nanoparticles.

    Science.gov (United States)

    Kudo, Shinpei; Nagasaki, Yukio

    2015-11-10

    In the immune system, macrophages in tumor tissue generate nitric oxide (NO), producing versatile effects including apoptosis of tumor cells, because inducible NO synthase (iNOS) in the cytoplasm of a macrophage produces NO using l-arginine as a substrate. Here, we propose novel NO-triggered immune therapeutics based on our newly designed nanoparticle system. We designed a poly(ethylene glycol)-block-poly(l-arginine) (i.e., PEG-b-P(l-Arg)) block copolymer and prepared polyion complex micelles (PEG-b-P(l-Arg)/m) composed of PEG-b-P(l-Arg) and chondroitin sulfate for systemic anticancer immunotherapy. iNOS treatment of PEG-b-P(l-Arg) did not generate NO, but NO molecules were detected after trypsin pretreatment, indicating that hydrolysis of P(l-Arg) to monomeric arginine was taking place in vitro. RAW264.7 macrophages abundantly generated NO from the PEG-b-P(l-Arg)/m in comparison with control micelles; this finding is indicative of robustness of the proposed method. It is interesting to note that systemic administration of PEG-b-P(l-Arg)/m had no noticeable adverse effects and suppressed the tumor growth rate in C26 tumor-bearing mice in a dose-dependent manner. Our newly designed nanoparticle-assisted arginine delivery system seems to hold promise as an NO-mediated anticancer immunotherapy. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Physical and Chemical Characterization of Therapeutic Iron Containing Materials: A Study of Several Superparamagnetic Drug Formulations with the β-FeOOH or Ferrihydrite Structure

    International Nuclear Information System (INIS)

    Funk, Felix; Long, Gary J.; Hautot, Dimitri; Buechi, Ruth; Christl, Iso; Weidler, Peter G.

    2001-01-01

    The effectiveness of therapeutically used iron compounds is related to their physical and chemical properties. Four different iron compounds used in oral, intravenous, and intramuscular therapy have been examined by X-ray powder diffraction, iron-57 Moessbauer spectroscopy, transmission electron microscopy, BET surface area measurement, potentiometric titration and studied through dissolution kinetics determinations using acid, reducing and chelating agents. All compounds are nanosized with particle diameters, as determined by X-ray diffraction, ranging from 1 to 4.1 nm. The superparamagnetic blocking temperatures, as determined by Moessbauer spectroscopy, indicate that the relative diameters of the aggregates range from 2.5 to 4.1 nm. Three of the iron compounds have an akaganeite-like structure, whereas one has a ferrihydrite-like structure. As powders the particles form large and dense aggregates which have a very low surface area on the order of 1 m 2 g -1 . There is evidence, however, that in a colloidal solution the surface area is increased by two to three orders of magnitude, presumably as a result of the break up of the aggregates. Iron release kinetics by acid, chelating and reducing agents reflect the high surface area, the size and crystallinity of the particles, and the presence of the protective carbohydrate layer coating the iron compound. Within a physiologically relevant time period, the iron release produced by acid or large chelating ligands is small. In contrast, iron is rapidly mobilized by small organic chelating agents, such as oxalate, or by chelate-forming reductants, such as thioglycolate

  14. Physical and Chemical Characterization of Therapeutic Iron Containing Materials: A Study of Several Superparamagnetic Drug Formulations with the β-FeOOH or Ferrihydrite Structure

    Science.gov (United States)

    Funk, Felix; Long, Gary J.; Hautot, Dimitri; Büchi, Ruth; Christl, Iso; Weidler, Peter G.

    2001-03-01

    The effectiveness of therapeutically used iron compounds is related to their physical and chemical properties. Four different iron compounds used in oral, intravenous, and intramuscular therapy have been examined by X-ray powder diffraction, iron-57 Mössbauer spectroscopy, transmission electron microscopy, BET surface area measurement, potentiometric titration and studied through dissolution kinetics determinations using acid, reducing and chelating agents. All compounds are nanosized with particle diameters, as determined by X-ray diffraction, ranging from 1 to 4.1 nm. The superparamagnetic blocking temperatures, as determined by Mössbauer spectroscopy, indicate that the relative diameters of the aggregates range from 2.5 to 4.1 nm. Three of the iron compounds have an akaganeite-like structure, whereas one has a ferrihydrite-like structure. As powders the particles form large and dense aggregates which have a very low surface area on the order of 1 m2 g-1. There is evidence, however, that in a colloidal solution the surface area is increased by two to three orders of magnitude, presumably as a result of the break up of the aggregates. Iron release kinetics by acid, chelating and reducing agents reflect the high surface area, the size and crystallinity of the particles, and the presence of the protective carbohydrate layer coating the iron compound. Within a physiologically relevant time period, the iron release produced by acid or large chelating ligands is small. In contrast, iron is rapidly mobilized by small organic chelating agents, such as oxalate, or by chelate-forming reductants, such as thioglycolate.

  15. Hemostatic granules and dressing prepared from formulations of carboxymethyl cellulose, kappa-carrageenan and polyethylene oxide crosslinked by gamma radiation

    Science.gov (United States)

    Barba, Bin Jeremiah D.; Aranilla, Charito T.; Relleve, Lorna S.; Cruz, Veriza Rita C.; Vista, Jeanina Richelle; Abad, Lucille V.

    2018-03-01

    Uncontrolled hemorrhage remains a persistent problem especially in anatomical areas where compression and tourniquet cannot be applied. Hemostatic agents are materials which can achieve control of bleeding in acute, life-threatening traumatic coagulopathy. In this study, we prepared biocompatible hydrogel-based hemostat crosslinked by ionizing radiation. Granules made from carboxymethyl cellulose and dressing from kappa carrageenan and polyethylene oxide were characterized by FT-IR, SEM, and gel analysis. Gamma radiation with a dose of 25 kGy was used for sterilization process. Stability studies indicate that the products remain effective with a shelf life of up to 18 months based on accelerated aging. Both hemostatic agents were demonstrated to be effective in vitro blood clotting assays showing a low blood clotting index, high platelet adhesion capacity and accelerated clotting time. Hemostat granules and dressing were also used in a femoral artery rat bleeding model where hemorrhage control was achieved in 90 s without compression and resulted in 100% survival rate after a 7 and 14-day observation.

  16. The interactive effects of various nitrogen fertiliser formulations applied to urine patches on nitrous oxide emissions in grassland

    Directory of Open Access Journals (Sweden)

    Krol D.J.

    2017-09-01

    Full Text Available Pasture-based livestock agriculture is a major source of greenhouse gas (GHG nitrous oxide (N2O. Although a body of research is available on the effect of urine patch N or fertiliser N on N2O emissions, limited data is available on the effect of fertiliser N applied to patches of urinary N, which can cover up to a fifth of the yearly grazed area. This study investigated whether the sum of N2O emissions from urine and a range of N fertilisers, calcium ammonium nitrate (CAN or urea ± urease inhibitor ± nitrification inhibitor, applied alone (disaggregated and re-aggregated approximated the N2O emission of urine and fertiliser N applied together (aggregated. Application of fertiliser to urine patches did not significantly increase either the cumulative yearly N2O emissions or the N2O emission factor in comparison to urine and fertiliser applied separately with the emissions re-aggregated. However, there was a consistent trend for approximately 20% underestimation of N2O loss generated from fertiliser and urine applied separately when compared to figures generated when urine and fertiliser were applied together. N2O emission factors from fertilisers were 0.02%, 0.06%, 0.17% and 0.25% from urea ± dicyandiamide (DCD, urea + N-(n-butyl thiophosphoric triamide (NBPT + DCD, urea + NBPT and urea, respectively, while the emission factor for urine alone was 0.33%. Calcium ammonium nitrate and urea did not interact differently with urine even when the urea included DCD. N2O losses could be reduced by switching from CAN to urea-based fertilisers.

  17. Formulation of chemically reactive foams for the dissolution of oxides polluting the secondary circuits of steam generators

    International Nuclear Information System (INIS)

    Provens, Helene

    1999-01-01

    The fouling of the Steam Generators (SG) secondary circuits, due to oxides deposits like magnetite (Fe 3 O 4 ), induces the degradation of the internal SG equipment, the reduction of the plant power, implying to clean these circuits. This operation made in liquid phase generates an important volume of effluents with an expensive cost of treatment. The use of a reactive foam allows the reduction of this volume by ten. Among the reactive tested, oxalic acid is the most efficient to dissolve a magnetite quantity of 10 g.l -1 , at ambient temperature for 24 hours, as imposed by the industrial wishes. The dissolution is not complete in our experimental conditions and is a complex reaction of autocatalytic type, composed of an acid attack, a reductive step, both followed by a slow diffusion. The surfactants generating the foam, which transport the reactive, are adsorbed on the magnetite but this affects weakly the dissolution. Its effectiveness is evaluated varying the experimental conditions. The wetting properties and the stability of the foam induce erosion and undissolved particles transport capacities, during its circulation into the SG. These particles trapped in the inter-bubble liquid films or carried by the piston effect of the foam bed, can be recovered on filters placed out of the SG. To quantify the transport, the influence of different parameters is studied: the more stable the foam is, the more important the transport is. Innocuousness tests showed that oxalic acid was not harmful for constitutive SG materials, either they were isolated or coupled. The cleaning by oxalic acid causes ferrous oxalates precipitation, representing 10 to 15 pc of the total iron quantity depending on the sample. A rinsing out with a foam containing 1 pc oxalic acid and 5 pc hydrogen peroxide allows the dissolution of these precipitates without corrosion problems. (author) [fr

  18. A theranostic prodrug delivery system based on Pt(IV) conjugated nano-graphene oxide with synergistic effect to enhance the therapeutic efficacy of Pt drug.

    Science.gov (United States)

    Li, Jingwen; Lyv, Zhonglin; Li, Yanli; Liu, Huan; Wang, Jinkui; Zhan, Wenjun; Chen, Hong; Chen, Huabing; Li, Xinming

    2015-05-01

    Due to their high NIR-optical absorption and high specific surface area, graphene oxide and graphene oxide-based nanocomposites have great potential in both drug delivery and photothermal therapy. In the work reported herein we successfully integrate a Pt(IV) complex (c,c,t-[Pt(NH3)2Cl2(OH)2]), PEGylated nano-graphene oxide (PEG-NGO), and a cell apoptosis sensor into a single platform to generate a multifunctional nanocomposite (PEG-NGO-Pt) which shows potential for targeted drug delivery and combined photothermal-chemotherapy under near infrared laser irradiation (NIR), and real-time monitoring of its therapeutic efficacy. Non-invasive imaging using a fluorescent probe immobilized on the GO shows an enhanced therapeutic effect of PEG-NGO-Pt in cancer treatment via apoptosis and cell death. Due to the enhanced cytotoxicity of cisplatin and the highly specific tumor targeting of PEG-NGO-Pt at elevated temperatures, this nanocomposite displays a synergistic effect in improving the therapeutic efficacy of the Pt drug with complete destruction of tumors, no tumor recurrence and minimal systemic toxicity in comparison with chemotherapy or photothermal treatment alone, highlighting the advantageous effects of integrating Pt(IV) with GO for anticancer treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Voltammetric Determination of Meloxicam in Pharmaceutical Formulation and Human Serum at Glassy Carbon Electrode Modified by Cysteic Acid Formed by Electrochemical Oxidation of L-cysteine

    Directory of Open Access Journals (Sweden)

    Xiao Ya Hu

    2005-09-01

    Full Text Available The improvement of electrochemical detection of meloxicam is presented bymodification of a glassy carbon electrode with anionic layer of cysteic acid providingelectrostatic accumulation of the analyte onto the electrode surface. The modificationformed by electrochemical oxidation of L-cysteine was performed by cycling potential incysteine solution. The anodic peak current obtained at 1.088 V (vs. Ag/AgCl byvoltammetry was linearly dependent on the meloxicam concentration in the range of 4.3 ×10-8 ~ 8.5 × 10-6 M in the B-R buffer solution (0.04 M, pH 1.86 with a correlationcoefficient of 0.999. The detection limit (S/N = 3 is 1.5 × 10-9 M. The low-cost modifiedelectrode shows good sensitivity, selectivity and stability and has been applied to thedetermination of meloxicam in pharmaceutical formulation and spiked serum withsatisfactory results. The electrochemical reaction mechanism of meloxicam was discussed.

  20. Skin beautification with oral non-hydrolized versions of carnosine and carcinine: Effective therapeutic management and cosmetic skincare solutions against oxidative glycation and free-radical production as a causal mechanism of diabetic complications and skin aging.

    Science.gov (United States)

    Babizhayev, Mark A; Deyev, Anatoliy I; Savel'yeva, Ekaterina L; Lankin, Vadim Z; Yegorov, Yegor E

    2012-10-01

    the generation of the cross-linked radical cation and the radical counteranion of methylglyoxal. Under aerobic conditions, molecular oxygen can then accept an electron from the methylglyoxal anion to generate the superoxide radical anion causing the propagation of oxidative stress chain reactions in the presence of transition metal ions. Carnosine stabilized from enzymatic hydrolysis, carcinine and leucyl-histidylhydrazide in patented formulations thereof, demonstrate the Schiff bases' transglycating activities concomitant with glycation site specific antioxidant activities and protection of proprietary antioxidant enzymes in the skin during aging and with diabetes lesions. During oral supplementation with stabilized from enzymatic hydrolysis carnosine (Can-C Plus® formulation), the skin parameters investigated showed a continuous and significant improvement in the active group during the 3 months of supplementation as compared to placebo. Visual investigation showed improvement of the overall skin appearance and a reduction of fine lines. No treatment-related side effects were reported. The finding that already-formed AGE cross-links can be pharmacologically severed and attendant pathology thereby reversed by non-hydrolized carnosine or carcinine in patented oral formulations thereof has broad implications for the skin beautification and therapeutics of the complications of diabetes and skin diseases associated with aging.

  1. First-in-man application of a novel therapeutic cancer vaccine formulation with the capacity to induce multi-functional T cell responses in ovarian, breast and prostate cancer patients

    Directory of Open Access Journals (Sweden)

    Berinstein Neil L

    2012-08-01

    Full Text Available Abstract Background DepoVaxTM is a novel non-emulsion depot-forming vaccine platform with the capacity to significantly enhance the immunogenicity of peptide cancer antigens. Naturally processed HLA-A2 restricted peptides presented by breast, ovarian and prostate cancer cells were used as antigens to create a therapeutic cancer vaccine, DPX-0907. Methods A phase I clinical study was designed to examine the safety and immune activating potential of DPX-0907 in advanced stage breast, ovarian and prostate cancer patients. A total of 23 late stage cancer patients were recruited and were divided into two dose/volume cohorts in a three immunization protocol. Results DPX-0907 was shown to be safe with injection site reactions being the most commonly reported adverse event. All breast cancer patients (3/3, most of ovarian (5/6 and one third of prostate (3/9 cancer patients exhibited detectable immune responses, resulting in a 61% immunological response rate. Immune responses were generally observed in patients with better disease control after their last prior treatment. Antigen-specific responses were detected in 73% of immune responders (44% of evaluable patients after the first vaccination. In 83% of immune responders (50% of evaluable patients, peptide-specific T cell responses were detected at ≥2 time points post vaccination with 64% of the responders (39% of evaluable patients showing evidence of immune persistence. Immune monitoring also demonstrated the generation of antigen-specific T cell memory with the ability to secrete multiple Type 1 cytokines. Conclusions The novel DepoVax formulation promotes multifunctional effector memory responses to peptide-based tumor associated antigens. The data supports the capacity of DPX-0907 to elicit Type-1 biased immune responses, warranting further clinical development of the vaccine. This study underscores the importance of applying vaccines in clinical settings in which patients are more likely to be

  2. Photodynamic Therapy Oxidative Stress as a Molecular Switch Controlling Therapeutic Gene Expression for the Treatment of Locally Recurrent Breast Carcinoma

    National Research Council Canada - National Science Library

    Gomer, Charles

    2002-01-01

    ... a procedure offering local tumoricidal activity. We have demonstrated that PDT-mediated oxidative stress is a strong transcriptional inducer of stress proteins belonging to the heat shock protein (hsp...

  3. Novel Formulations for Antimicrobial Peptides

    Directory of Open Access Journals (Sweden)

    Ana Maria Carmona-Ribeiro

    2014-10-01

    Full Text Available Peptides in general hold much promise as a major ingredient in novel supramolecular assemblies. They may become essential in vaccine design, antimicrobial chemotherapy, cancer immunotherapy, food preservation, organs transplants, design of novel materials for dentistry, formulations against diabetes and other important strategical applications. This review discusses how novel formulations may improve the therapeutic index of antimicrobial peptides by protecting their activity and improving their bioavailability. The diversity of novel formulations using lipids, liposomes, nanoparticles, polymers, micelles, etc., within the limits of nanotechnology may also provide novel applications going beyond antimicrobial chemotherapy.

  4. Novel Formulations for Antimicrobial Peptides

    Science.gov (United States)

    Carmona-Ribeiro, Ana Maria; Carrasco, Letícia Dias de Melo

    2014-01-01

    Peptides in general hold much promise as a major ingredient in novel supramolecular assemblies. They may become essential in vaccine design, antimicrobial chemotherapy, cancer immunotherapy, food preservation, organs transplants, design of novel materials for dentistry, formulations against diabetes and other important strategical applications. This review discusses how novel formulations may improve the therapeutic index of antimicrobial peptides by protecting their activity and improving their bioavailability. The diversity of novel formulations using lipids, liposomes, nanoparticles, polymers, micelles, etc., within the limits of nanotechnology may also provide novel applications going beyond antimicrobial chemotherapy. PMID:25302615

  5. Therapeutic effect of methanolic extract of Laportea aestuans (L.) Chew, on oxidative stress in the brain of male Wistar rats

    Science.gov (United States)

    Elizabeth, Omotosho Omolola; Olawumi, Ogunlade Oladipupo

    2018-04-01

    The aim of this study was to assess the effect of diclofenac-induced oxidative stress in the brain of Wistar rats. The experiment was carried out using thirty-six rats. Six groups contained six rats in each. The first group being the control group received 1ml of gum acacia which is the vehicle. Groups 2 to 6 were induced with oxidative stress by oral administration of 40 mg/kg body weight of diclofenac and pretreated as follows: group 2 received only diclofenac, group 3 with 200 mg/kg body weight of methanolic extract of Laportea aestuans (L.) Chew, group 4 with 400 mg/kg body weight of Laportea aestuans extract, group 5 with 800 mg/kg body weight of Laportea aestuans and group 6 with 50 mg/kg body weight of cimetidine. The pretreatment was carried out for a period of seven days after which oxidative stress was induced. The animals were thereafter sacrificed and brain was excised. Antioxidant enzymes and molecules such as superoxide dismutase, catalase, glutathione, levels of malondialdehyde and protein carbonyl were assayed by standard methods. The results showed significant increases in glutathione level and activities of catalase, superoxide dismutase and significant decrease in lipid peroxidation and protein carbonyl in groups 3 to 5 when compared to group 2. This shows that the methanolic extract of Laportea aestuans has a protective effect on the brain against oxidative stress.

  6. Glyceraldehyde-3-phosphate dehydrogenase aggregation inhibitor peptide: A potential therapeutic strategy against oxidative stress-induced cell death.

    Science.gov (United States)

    Itakura, Masanori; Nakajima, Hidemitsu; Semi, Yuko; Higashida, Shusaku; Azuma, Yasu-Taka; Takeuchi, Tadayoshi

    2015-11-13

    The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has multiple functions, including mediating oxidative stress-induced neuronal cell death. This process is associated with disulfide-bonded GAPDH aggregation. Some reports suggest a link between GAPDH and the pathogenesis of several oxidative stress-related diseases. However, the pathological significance of GAPDH aggregation in disease pathogenesis remains unclear due to the lack of an effective GAPDH aggregation inhibitor. In this study, we identified a GAPDH aggregation inhibitor (GAI) peptide and evaluated its biological profile. The decapeptide GAI specifically inhibited GAPDH aggregation in a concentration-dependent manner. Additionally, the GAI peptide did not affect GAPDH glycolytic activity or cell viability. The GAI peptide also exerted a protective effect against oxidative stress-induced cell death in SH-SY5Y cells. This peptide could potentially serve as a tool to investigate GAPDH aggregation-related neurodegenerative and neuropsychiatric disorders and as a possible therapy for diseases associated with oxidative stress-induced cell death. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. The role of oxidative stress in EBV lytic reactivation, radioresistance and the potential preventive and therapeutic implications.

    Science.gov (United States)

    Hu, Jianmin; Li, Hongde; Luo, Xiangjian; Li, Yueshuo; Bode, Ann; Cao, Ya

    2017-11-01

    Epstein-Barr virus (EBV) is an important cancer causing virus. Cancer associated with EBV account for approximately 1.5% of all cancers, and represent 1.8% of all cancer deaths worldwide. EBV reactivation plays an important role in the development of EBV-related diseases and is closely related with patients' survival and clinical stages of EBV-related cancers. The therapy regarding to EBV-related cancers is very urgent, especially in endemic areas. Generating oxidative stress is a critical mechanism by which host cells defend against infection by virus. In addition, ROS-mediated oxidative stress plays a significant but paradoxical role acting as a "double-edged sword" to regulate cellular response to radiation, which is the main therapy strategy for EBV-related cancers, especially nasopharyngeal carcinoma. Therefore, in this review we primarily discuss the possible interplay among the oxidative stress, EBV lytic reactivation and radioresistance. Understanding the role of oxidative stress in EBV lytic reactivation and radioresistance will assist in the development of effective strategies for prevention and treatment of EBV-related cancers. © 2017 UICC.

  8. Improving anaerobic digestion of pig manure by adding in the same reactor a stabilizing agent formulated with low-grade magnesium oxide

    International Nuclear Information System (INIS)

    Romero-Güiza, M.S.; Astals, S.; Chimenos, J.M.; Martínez, M.; Mata-Alvarez, J.

    2014-01-01

    Struvite precipitation and pig manure anaerobic digestion were coupled in the same reactor in order to mitigate the inhibitory effect of free ammonia and avoid precipitator costs. The stabilizing agent used to facilitate struvite precipitation was formulated with low-grade magnesium oxide by-product; an approach that would notably reduce struvite processing costs. The interaction between pig manure and stabilizing agent was analyzed in batch experiments, on a wide range of stabilizing agent additions from 5 to 100 kg m −3 . The monitoring of the pH and ammonia removal during 24 h showed the high capacity of the stabilizing agent to remove ammonia; removal efficiencies above 80% were obtained from 40 kg m −3 . However, a long-term anaerobic digester operation was required to assess the feasibility of the process and to ensure that the stabilizing agent does not introduce any harmful compound for the anaerobic biomass. In this vein, the addition of 5 and 30 kg m −3 of the stabilizing agent in a pig manure continuous digester resulted in a 25% (0.17 m 3  kg −1 ) and a 40% (0.19 m 3  kg −1 ) increase in methane production per mass of volatile solid, respectively, when compared with the reference digester (0.13 m 3  kg −1 ). Moreover, the stability of the process during four hydraulic retention times guarantees that the stabilizing agent did not exert a negative effect on the consortium of microorganisms. Finally, scanning electron microscopy and X-ray diffraction analysis confirmed the presence of struvite as well as two precipitation mechanisms, struvite precipitation on the stabilizing agent surface and in the bulk solution. - Highlights: • Anaerobic digestion and struvite precipitation were satisfactorily coupled. • The stabilizing agent showed high ammonia removals efficiencies. • The stabilizing agent improved the methane production of a pig manure digester. • The stabilizing agent does not introduce harmful compound for the

  9. Human nitric oxide biomarker as potential NO donor in conjunction with superparamagnetic iron oxide @ gold core shell nanoparticles for cancer therapeutics.

    Science.gov (United States)

    Singh, Nimisha; Patel, Khushbu; Sahoo, Suban K; Kumar, Rajender

    2018-03-01

    Nitric oxide releasing superparamagnetic (Fe 3 O 4 -Au@NTHP) nanoparticles were synthesized by conjugation of human biomarker of nitric oxide, N-nitrosothioproline with iron oxide-gold (Fe 3 O 4 -Au) core shell nanoparticles. The structure and morphology of the prepared nanoparticles were confirmed by ATR-FTIR, HR-TEM, EDAX, XPS, DLS and VSM measurements. N-nitrosothioproline is a natural molecule and nontoxic to humans. Thus, the core shell nanoparticles prepared were highly biocompatible. The prepared Fe 3 O 4 -Au@NTHP nanoparticles also provided an excellent release of nitric oxide in dark and upon light irradiation for cancer treatment. The amount of NO release was controllable with the wavelength of light and time of irradiation. The developed nanoparticles provided efficient cellular uptake and good cytotoxicity in picomolar range when tested on HeLa cancerous cells. These nanoparticles on account of their controllable NO release can also be used to release small amount of NO for killing cancerous cells without any toxic effect. Furthermore, the magnetic and photochemical properties of these nanoparticles provides dual platform for magneto therapy and phototherapy for cancer treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Effects of cryotherapy combined with therapeutic ultrasound on oxidative stress and tissue damage after musculoskeletal contusion in rats.

    Science.gov (United States)

    Martins, C N; Moraes, M B; Hauck, M; Guerreiro, L F; Rossato, D D; Varela, A S; da Rosa, C E; Signori, L U

    2016-12-01

    To investigate the combined effects of cryotherapy and pulsed ultrasound therapy (PUT) on oxidative stress parameters, tissue damage markers and systemic inflammation after musculoskeletal injury. Experimental animal study. Research laboratory. Seventy male Wistar rats were divided into five groups: control, lesion, cryotherapy, PUT, and cryotherapy+PUT. The gastrocnemius muscle was injured by mechanical crushing. Cryotherapy was applied immediately after injury (immersion in water at 10°C for 20minutes). PUT was commenced 24hours after injury (1MHz, 0.4W/cm 2SPTA , 20% duty cycle, 5minutes). All animals were treated every 8hours for 3 days. Oxidative stress in muscle was evaluated by concentration of reactive oxygen species (ROS), lipid peroxidation (LPO), anti-oxidant capacity against peroxyl radicals (ACAP) and catalase. Plasma levels of creatine kinase (CK), lactate dehydrogenase (LDH) and C-reactive protein (CRP) were assessed. When applied individually, cryotherapy and PUT reduced CK, LDH, CRP and LPO caused by muscle damage. Cryotherapy+PUT in combination maintained the previous results, caused a reduction in ROS [P=0.005, mean difference -0.9×10 -8 relative area, 95% confidence interval (CI) -0.2 to -1.9], and increased ACAP {P=0.007, mean difference 0.34 1/[relative area with/without 2,2-azobis(2-methylpropionamidine)dihydrochloride], 95% CI 0.07 to 0.61} and catalase (P=0.002, mean difference 0.41units/mg protein, 95% CI 0.09 to 0.73) compared with the lesion group. Cryotherapy+PUT in combination reduced oxidative stress in muscle, contributing to a reduction in adjacent damage and tissue repair. Copyright © 2016 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

  11. 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.

  12. Enhancement of solubility and therapeutic potential of poorly soluble lovastatin by SMEDDS formulation adsorbed on directly compressed spray dried magnesium aluminometasilicate liquid loadable tablets: A study in diet induced hyperlipidemic rabbits

    Directory of Open Access Journals (Sweden)

    Mohd Javed Qureshi

    2015-02-01

    Full Text Available The aim of present study was to formulate and evaluate a self-microemulsifying drug delivery systems (SMEDDS containing lovastatin and to further explore the ability of porous Neusilin® US2 tablet as a solid carrier for SMEDDS. SMEDDS formulations of varying proportions of peceol, cremophor RH 40 and transcutol-P were selected and subjected to in-vitro evaluation, including dispersibility studies, droplet size, zeta potential measurement and release studies. The results indicated that the drug release profile of lovastatin from SMEDDS formulations was statistically significantly higher (p-value < 0.05 than the plain lovastatin powder. Thermodynamic stability studies also confirmed the stability of the prepared SMEDDS formulations. The optimized formulation, which consists of 12% of peceol, 44% of cremophor RH 40, and 44% of transcutol-P was loaded into directly compressed liquid loadable tablet of Neusilin® US2 by simple adsorption method. In order to determine the ability of Neusilin® US2 as a suitable carrier pharmacodynamics study were also carried out in healthy diet induced hyperlipidemic rabbits. Animals were administered with both liquid SMEDDS and solid SMEDDS as well. From the results obtained, Neusilin® was found to be a suitable carrier for SMEDDS and was equally effective in reducing the elevated lipid profile. In conclusion, liquid loadable tablet (LLT is predicted to be a promising technique to deliver a liquid formulation in solid state.

  13. Thioredoxin-1 overexpression in transgenic mice attenuates streptozotocin-induced diabetic osteopenia: a novel role of oxidative stress and therapeutic implications.

    Science.gov (United States)

    Hamada, Yasuhiro; Fujii, Hideki; Kitazawa, Riko; Yodoi, Junji; Kitazawa, Sohei; Fukagawa, Masafumi

    2009-05-01

    . Suppression of increased oxidative stress by TRX induction could be a potential therapeutic approach for diabetic osteopenia.

  14. Nitric oxide modulation of the basal ganglia circuitry: therapeutic implication for Parkinson's disease and other motor disorders.

    Science.gov (United States)

    Pierucci, Massimo; Galati, Salvatore; Valentino, Mario; Di Matteo, Vincenzo; Benigno, Arcangelo; Pitruzzella, Alessandro; Muscat, Richard; Di Giovanni, Giuseppe

    2011-11-01

    Several recent studies have emphasized a crucial role for the nitrergic system in movement control and the pathophysiology of the basal ganglia (BG). These observations are supported by anatomical evidence demonstrating the presence of nitric oxide synthase (NOS) in all the basal ganglia nuclei. In fact, nitrergic terminals have been reported to make synaptic contacts with both substantia nigra dopamine-containing neurons and their terminal areas such as the striatum, the globus pallidus and the subthalamus. These brain areas contain a high expression of nitric oxide (NO)-producing neurons, with the striatum having the greatest number, together with important NO afferent input. In this paper, the distribution of NO in the BG nuclei will be described. Furthermore, evidence demonstrating the nitrergic control of BG activity will be reviewed. The new avenues that the increasing knowledge of NO in motor control has opened for exploring the pathophysiology and pharmacology of Parkinson's disease and other movement disorders will be discussed. For example, inhibition of striatal NO/guanosine monophosphate signal pathway by phosphodiesterases seems to be effective in levodopa-induced dyskinesia. However, the results of experimental studies have to be interpreted with caution given the complexities of nitrergic signalling and the limitations of animal models. Nevertheless, the NO system represents a promising pharmacological intervention for treating Parkinson's disease and related disorders.

  15. Ameliorative effect of riboflavin on hyperglycemia, oxidative stress and DNA damage in type-2 diabetic mice: Mechanistic and therapeutic strategies.

    Science.gov (United States)

    Alam, Md Maroof; Iqbal, Sarah; Naseem, Imrana

    2015-10-15

    Increasing evidence in both experimental and clinical studies suggests that oxidative stress play a major role in the pathogenesis of type-2 diabetes mellitus (T2DM). Abnormally high levels of free radicals and the simultaneous decline of antioxidant defence mechanisms can lead to damage of cellular organelles and enzymes. Riboflavin constitutes an essential nutrient for humans and is also an important food additive for animals. It is a precursor of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) which serves as a coenzyme for several enzymes. The aim of this study was to observe the effects of illuminated and non-illuminated riboflavin in a diabetic mice model. The protocol included treatment of diabetic mice with illuminated RF and a control set without light. To our surprise, group receiving RF without light gave better results in a dose dependent manner. Significant amelioration of oxidative stress was observed with an increased glucose uptake in skeletal muscles and white adipose tissue. Histological studies showed recovery in the liver and kidney tissue injury. Cellular DNA damage was also recovered. Therefore, it is suggested that supplementation with dietary riboflavin might help in the reduction of diabetic complications. A possible mechanism of action is also proposed. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Carbon Nanoparticles decorated with cupric oxide Nanoparticles prepared by laser ablation in liquid as an antibacterial therapeutic agent

    Science.gov (United States)

    Khashan, Khawla S.; Jabir, Majid S.; Abdulameer, Farah A.

    2018-03-01

    Carbon nanoparticles (CNPs) decorated with cupric oxide nanoparticles (CuO NPs) were prepared by laser ablation in water, and their antibacterial activity was examined. X-ray diffraction measurements demonstrated the presence of carbon phases and different CuO phases, and results were confirmed by Fourier transform infrared analysis. Energy- Dispersive spectra showed the presence of C, O, and Cu in the final product. Transmission electron micrographs revealed that the CNPs were 10-80 nm in size and spherical; after being decorated with CuO NPs, particles became 5-50 nm in size and uniform in shape. The absorption spectrum of decorated Nanoparticles indicated the appearance of a new peak at 254-264 nm in addition to the fundamental peak at 228 nm. We then examined the antibacterial activity of the decorated CNPs for both gram-negative and -positive bacteria using the agar-well-diffusion method. The mode of action was determined using acridine orange-ethidium bromide staining to detect reactive oxygen species, and bacterial morphological change was studied by scanning electron microscopy. Results showed that CNPs decorated with 43% CuO NPs had the highest antibacterial activity for gram-positive bacteria. The CNPs acted on the cytoplasmic membrane and nucleic acid of bacteria, which led to a loss of cell-wall integrity, increased cell-wall permeability, and nucleic acid damage. The results offer a novel way to synthesis Carbon nanoparticles decorated with cupric oxide nanoparticles and could use them as novel antibacterial agent in future for pharmaceutical and biomedical applications.

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

    Directory of Open Access Journals (Sweden)

    Monir Moradzadeh Khiavi

    2015-06-01

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

  18. Oxidizing gel formulation for nuclear decontamination: rheological and acidic properties of the organic matrix and its ozonolysis; Formulation d'un gel oxydant a matrice organique applicable a la decontamination nucleaire: proprietes rheologiques, acido-basiques et ozonolyse de la matrice

    Energy Technology Data Exchange (ETDEWEB)

    Rouy, E

    2003-10-15

    An acidic and oxidizing gel was formulated with a purely organic matrix, xanthan gum, at low concentrations (1 to 2 wt %). This polymer gel was investigated in various media (aqueous, acidic and ceric) by means of rheology: shear thinning behaviour, thixotropy, yield stress... Evidences of unexpected rheological properties in highly concentrated media show that xanthan is quite convenient for industrial projection of this type of gel on metallic walls in nuclear plants, notwithstanding its time-limited resistance to oxidation (about a few hours). Complexation mechanisms between ceric species and polar sites of the polymer led us to characterise acidic properties of our xanthan sample by potentiometric titration and {sup 1}H NMR techniques. The matrix was finally treated by ozonolysis to suppress organic residues, as required to handle nuclear wastes. In acidic medium, ozonolysis of the gel was achieved successfully while in acidic and ceric medium this process showed limited efficiency, needing further investigation to be clarified. (author)

  19. Oxidizing gel formulation for nuclear decontamination: rheological and acidic properties of the organic matrix and its ozonolysis; Formulation d'un gel oxydant a matrice organique applicable a la decontamination nucleaire: proprietes rheologiques, acido-basiques et ozonolyse de la matrice

    Energy Technology Data Exchange (ETDEWEB)

    Rouy, E

    2003-10-15

    An acidic and oxidizing gel was formulated with a purely organic matrix, xanthan gum, at low concentrations (1 to 2 wt %). This polymer gel was investigated in various media (aqueous, acidic and ceric) by means of rheology: shear thinning behaviour, thixotropy, yield stress... Evidences of unexpected rheological properties in highly concentrated media show that xanthan is quite convenient for industrial projection of this type of gel on metallic walls in nuclear plants, notwithstanding its time-limited resistance to oxidation (about a few hours). Complexation mechanisms between ceric species and polar sites of the polymer led us to characterise acidic properties of our xanthan sample by potentiometric titration and {sup 1}H NMR techniques. The matrix was finally treated by ozonolysis to suppress organic residues, as required to handle nuclear wastes. In acidic medium, ozonolysis of the gel was achieved successfully while in acidic and ceric medium this process showed limited efficiency, needing further investigation to be clarified. (author)

  20. New Nitric Oxide Donor NCX 1443: Therapeutic Effects on Pulmonary Hypertension in the SAD Mouse Model of Sickle Cell Disease.

    Science.gov (United States)

    Abid, Shariq; Kebe, Kanny; Houssaïni, Amal; Tomberli, Françoise; Marcos, Elisabeth; Bizard, Emilie; Breau, Marielle; Parpaleix, Aurelien; Tissot, Claire-Marie; Maitre, Bernard; Lipskaia, Larissa; Derumeaux, Genevieve; Bastia, Elena; Mekontso-Dessap, Armand; Adnot, Serge

    2018-05-01

    Nitric oxide (NO) donors may be useful for treating pulmonary hypertension (PH) complicating sickle cell disease (SCD), as endogenous NO is inactivated by hemoglobin released by intravascular hemolysis. Here, we investigated the effects of the new NO donor NCX1443 on PH in transgenic SAD mice, which exhibit mild SCD without severe hemolytic anemia. In SAD and wild-type (WT) mice, the pulmonary pressure response to acute hypoxia was similar and was abolished by 100 mg/kg NCX1443. The level of PH was also similar in SAD and WT mice exposed to chronic hypoxia (9% O2) alone or with SU5416 and was similarly reduced by daily NCX1443 gavage. Compared with WT mice, SAD mice exhibited higher levels of HO-1, endothelial NO synthase, and PDE5 but similar levels of lung cyclic guanosine monophosphate. Cultured pulmonary artery smooth muscle cells from SAD mice grew faster than those from WT mice and had higher PDE5 protein levels. Combining NCX1443 and a PDE5 inhibitor suppressed the growth rate difference between SAD and WT cells and induced a larger reduction in hypoxic PH severity in SAD than in WT mice. By amplifying endogenous protective mechanisms, NCX1443 in combination with PDE5 inhibition may prove useful for treating PH complicating SCD.

  1. Monitoring the Therapeutic and Protective Role of the Anti oxidative Nutritional Factor β Carotene in gamma-Irradiated Rats

    International Nuclear Information System (INIS)

    Tawfik, S.S.; Mansour, H.H.

    2008-01-01

    Carotenoids are those substances, synthesized, only in plants that serve to protect the plants from free radicals. β-carotene, one of the carotenoids, has been thought to be of value to humans and other species, not only as precursors to vitamin A, but also for having excellent antioxidant properties. Four groups of rats were used to gain insight into the protective action of carotenes: control, β-carotene treated (30 mg/ kg body wt for 10 days), irradiated (4 fractions, each of 1.5 Gy gamma-rays during 10 days) and protracted group: rats received the same fractionated gamma-rays at the same time gavaged with β-carotene along the 10 days. Irradiated rats revealed significant decreases in p-carotene and glutathione (GSH) concentrations and significant increases in the activities of blood alkaline phosphatase (ALP), acid phosphatase (ACP), alanine transaminase (ALT), gamma-glutamyl transferase (GGT), catalase and contents of blood thiobarbituric acid-reactive substances (TBARS). In liver , tissue, TBARS content and catalase activity were raised while GSH was declined. The oral intake of β-carotene to irradiated rats was found to maintain the parameters measured near the control mean levels; i.e., increased content of blood β-carotene and GSH and modulated activities of ALP, ACP, ALT, GGT, catalase and TBARS level. It also, modulated the alterations of liver TBARS, catalase and GSH. Conclusion: β-carotene therapy significantly modulates oxidative damage induced by ionising radiation in rats

  2. Cream formulation impact on topical administration of engineered colloidal nanoparticles.

    Directory of Open Access Journals (Sweden)

    Benedetta Santini

    Full Text Available In order to minimize the impact of systemic toxicity of drugs in the treatment of local acute and chronic inflammatory reactions, the achievement of reliable and efficient delivery of therapeutics in/through the skin is highly recommended. While the use of nanoparticles is now an established practice for drug intravenous targeted delivery, their transdermal penetration is still poorly understood and this important administration route remains almost unexplored. In the present study, we have synthesized magnetic (iron oxide nanoparticles (MNP coated with an amphiphilic polymer, developed a water-in-oil emulsion formulation for their topical administration and compared the skin penetration routes with the same nanoparticles deposited as a colloidal suspension. Transmission and scanning electron microscopies provided ultrastructural evidence that the amphiphilic nanoparticles (PMNP cream formulation allowed the efficient penetration through all the skin layers with a controllable kinetics compared to suspension formulation. In addition to the preferential follicular pathway, also the intracellular and intercellular routes were involved. PMNP that crossed all skin layers were quantified by inductively coupled plasma mass spectrometry. The obtained data suggests that combining PMNP amphiphilic character with cream formulation improves the intradermal penetration of nanoparticles. While PMNP administration in living mice via aqueous suspension resulted in preferential nanoparticle capture by phagocytes and migration to draining lymph nodes, cream formulation favored uptake by all the analyzed dermis cell types, including hematopoietic and non-hematopoietic. Unlike aqueous suspension, cream formulation also favored the maintenance of nanoparticles in the dermal architecture avoiding their dispersion and migration to draining lymph nodes via afferent lymphatics.

  3. 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.

  4. Enhanced Therapeutic Potential of Nano-Curcumin Against Subarachnoid Hemorrhage-Induced Blood-Brain Barrier Disruption Through Inhibition of Inflammatory Response and Oxidative Stress.

    Science.gov (United States)

    Zhang, Zong-Yong; Jiang, Ming; Fang, Jie; Yang, Ming-Feng; Zhang, Shuai; Yin, Yan-Xin; Li, Da-Wei; Mao, Lei-Lei; Fu, Xiao-Yan; Hou, Ya-Jun; Fu, Xiao-Ting; Fan, Cun-Dong; Sun, Bao-Liang

    2017-01-01

    Curcumin and nano-curcumin both exhibit neuroprotective effects in early brain injury (EBI) after experimental subarachnoid hemorrhage (SAH). However, the mechanism that whether curcumin and its nanoparticles affect the blood-brain barrier (BBB) following SAH remains unclear. This study investigated the effect of curcumin and the poly(lactide-co-glycolide) (PLGA)-encapsulated curcumin nanoparticles (Cur-NPs) on BBB disruption and evaluated the possible mechanism underlying BBB dysfunction in EBI using the endovascular perforation rat SAH model. The results indicated that Cur-NPs showed enhanced therapeutic effects than that of curcumin in improving neurological function, reducing brain water content, and Evans blue dye extravasation after SAH. Mechanically, Cur-NPs attenuated BBB dysfunction after SAH by preventing the disruption of tight junction protein (ZO-1, occludin, and claudin-5). Cur-NPs also up-regulated glutamate transporter-1 and attenuated glutamate concentration of cerebrospinal fluid following SAH. Moreover, inhibition of inflammatory response and microglia activation both contributed to Cur-NPs' protective effects. Additionally, Cur-NPs markedly suppressed SAH-mediated oxidative stress and eventually reversed SAH-induced cell apoptosis in rats. Our findings revealed that the strategy of using Cur-NPs could be a promising way in improving neurological function in EBI after experimental rat SAH.

  5. Lipid Replacement Therapy: a Functional Food Approach with New Formulations for Reducing Cellular Oxidative Damage, Cancer-Associated Fatigue and the Adverse Effects of Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Garth L. Nicolson

    2011-04-01

    Full Text Available Backgroud:Cancer-associated fatigue and the chronic adverse effects of cancer therapy can be reduced by Lipid Replacement Therapy (LRT using membrane phospholipid mixtures given as food supplements.Methods:This is a review of the published literature on LRT and its uses.Results: LRT significantly reduced fatigue in cancer patients as well as patients suffering from chronic fatiguing illnesses and other medical conditions. It also reduced the adverse effects of chemotherapy, resulting in improvements in incidence of fatigue, nausea, diarrhea, impaired taste, constipation, insomnia and other quality of life indicators. In other diseases, such as chronic fatigue syndrome, fibromyalgia syndrome and other chronic fatiguing illnesses, LRT reduced fatigue by 35.5-43.1% in different clinical trials and increased mitochondrial function.Conclusions: LRT formulations appear to be useful as non-toxic dietary supplements for direct use or placed in functional foods to reduce fatigue and restore mitochondrial and other cellular membrane functions. Formulations of LRT phospholipids are suitable for addition to variousfood products for the treatment of a variety of chronic illnesses as well as their application inanti-aging and other health supplements and products.

  6. A natural pharma standard supplement formulation to control treatment-related toxicity and oxidative stress in genitourinary cancer: a preliminary study.

    Science.gov (United States)

    Ledda, A; Belcaro, G; Dugall, M; Luzzi, R; Hosoi, M; Feragalli, B; Cotellese, R; Cosentino, V; Cosentino, M; Eggenhoffner, R; Pellizzato, M; Fratter, A; Giacomelli, L

    2017-09-01

    Oncological treatments are associated with toxicities that may decrease compliance to treatment in most genitourinary cancer patients. Supplementation with pharmaceutical-standardized supplement may be a supplementary method to control the side effects after chemo- and radiotherapy and the increased oxidative stress associated to treatments. This registry study evaluated a natural combination of supplements containing curcumin, cordyceps, and astaxanthin (Oncotris™) used as supplementary management in genitourinary cancer patients who had undergone oncological therapy. Patients with genitourinary cancers (prostate or bladder malignancies) who had undergone and completed cancer treatments (radiotherapy, chemotherapy or intravesical immunotherapy with increased oxidative stress and residual symptoms) were recruited in this registry, supplement study. Registry subjects (n = 61) freely decided to follow either a standard management (SM) (control group = 35) or SM plus oral daily supplementation (supplement group = 26). Evaluation of severity of treatment-related residual side effects, blood count test, prostate-specific antigen (PSA) test and plasma free radicals (oxidative stress) were performed at inclusion and at the end of the observational period (6 weeks). Two patients dropped out during the registry. Therefore, the analysis included 59 participants: 26 individuals in the supplementation group and 33 in the control group. In the supplement group, the intensity of signs and symptoms (treatment-related) and residual side effects significantly decreased at 6 weeks: minimal changes were observed in controls. Supplementation with Oncotris™ was associated with a significant improvement in blood cell count and with a decreased level of plasmatic PSA and oxidative stress. Naturally-derived supplements, specifically Oncotris™ (patent pending), could support the body to overcome the treatment-related toxicities - and the relative oxidative stress in cancer patients.

  7. Crystallization Formulation Lab

    Data.gov (United States)

    Federal Laboratory Consortium — The Crystallization Formulation Lab fills a critical need in the process development and optimization of current and new explosives and energetic formulations. The...

  8. Submicron and nano formulations of titanium dioxide and zinc oxide stimulate unique cellular toxicological responses in the green microalga Chlamydomonas reinhardtii

    Energy Technology Data Exchange (ETDEWEB)

    Gunawan, Cindy, E-mail: c.gunawan@unsw.edu.au [ARC Centre of Excellence for Functional Nanomaterials, School of Chemical Engineering, The University of New South Wales, Sydney, NSW (Australia); Sirimanoonphan, Aunchisa [ARC Centre of Excellence for Functional Nanomaterials, School of Chemical Engineering, The University of New South Wales, Sydney, NSW (Australia); Teoh, Wey Yang [Clean Energy and Nanotechnology (CLEAN) Laboratory, School of Energy and Environment, City University of Hong Kong, Kowloon, Hong Kong Special Administrative Region (Hong Kong); Marquis, Christopher P., E-mail: c.marquis@unsw.edu.au [School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW (Australia); Amal, Rose [ARC Centre of Excellence for Functional Nanomaterials, School of Chemical Engineering, The University of New South Wales, Sydney, NSW (Australia)

    2013-09-15

    Highlights: • Uptake of TiO{sub 2} solids by C. reinhardtii generates ROS as an early stress response. • Submicron and nanoTiO{sub 2} exhibit benign effect on cell proliferation. • Uptake of ZnO solids and leached zinc by C. reinhardtii inhibit the alga growth. • No cellular oxidative stress is detected with submicron and nano ZnO exposure. • The toxicity of particles is not necessarily mediated by cellular oxidative stress. -- Abstract: The work investigates the eco-cytoxicity of submicron and nano TiO{sub 2} and ZnO, arising from the unique interactions of freshwater microalga Chlamydomonas reinhardtii to soluble and undissolved components of the metal oxides. In a freshwater medium, submicron and nano TiO{sub 2} exist as suspended aggregates with no-observable leaching. Submicron and nano ZnO undergo comparable concentration-dependent fractional leaching, and exist as dissolved zinc and aggregates of undissolved ZnO. Cellular internalisation of solid TiO{sub 2} stimulates cellular ROS generation as an early stress response. The cellular redox imbalance was observed for both submicron and nano TiO{sub 2} exposure, despite exhibiting benign effects on the alga proliferation (8-day EC50 > 100 mg TiO{sub 2}/L). Parallel exposure of C. reinhardtii to submicron and nano ZnO saw cellular uptake of both the leached zinc and solid ZnO and resulting in inhibition of the alga growth (8-day EC50 ≥ 0.01 mg ZnO/L). Despite the sensitivity, no zinc-induced cellular ROS generation was detected, even at 100 mg ZnO/L exposure. Taken together, the observations confront the generally accepted paradigm of cellular oxidative stress-mediated cytotoxicity of particles. The knowledge of speciation of particles and the corresponding stimulation of unique cellular responses and cytotoxicity is vital for assessment of the environmental implications of these materials.

  9. Submicron and nano formulations of titanium dioxide and zinc oxide stimulate unique cellular toxicological responses in the green microalga Chlamydomonas reinhardtii

    International Nuclear Information System (INIS)

    Gunawan, Cindy; Sirimanoonphan, Aunchisa; Teoh, Wey Yang; Marquis, Christopher P.; Amal, Rose

    2013-01-01

    Highlights: • Uptake of TiO 2 solids by C. reinhardtii generates ROS as an early stress response. • Submicron and nanoTiO 2 exhibit benign effect on cell proliferation. • Uptake of ZnO solids and leached zinc by C. reinhardtii inhibit the alga growth. • No cellular oxidative stress is detected with submicron and nano ZnO exposure. • The toxicity of particles is not necessarily mediated by cellular oxidative stress. -- Abstract: The work investigates the eco-cytoxicity of submicron and nano TiO 2 and ZnO, arising from the unique interactions of freshwater microalga Chlamydomonas reinhardtii to soluble and undissolved components of the metal oxides. In a freshwater medium, submicron and nano TiO 2 exist as suspended aggregates with no-observable leaching. Submicron and nano ZnO undergo comparable concentration-dependent fractional leaching, and exist as dissolved zinc and aggregates of undissolved ZnO. Cellular internalisation of solid TiO 2 stimulates cellular ROS generation as an early stress response. The cellular redox imbalance was observed for both submicron and nano TiO 2 exposure, despite exhibiting benign effects on the alga proliferation (8-day EC50 > 100 mg TiO 2 /L). Parallel exposure of C. reinhardtii to submicron and nano ZnO saw cellular uptake of both the leached zinc and solid ZnO and resulting in inhibition of the alga growth (8-day EC50 ≥ 0.01 mg ZnO/L). Despite the sensitivity, no zinc-induced cellular ROS generation was detected, even at 100 mg ZnO/L exposure. Taken together, the observations confront the generally accepted paradigm of cellular oxidative stress-mediated cytotoxicity of particles. The knowledge of speciation of particles and the corresponding stimulation of unique cellular responses and cytotoxicity is vital for assessment of the environmental implications of these materials

  10. A coupled transport and solid mechanics formulation with improved reaction kinetics parameters for modeling oxidation and decomposition in a uranium hydride bed.

    Energy Technology Data Exchange (ETDEWEB)

    Salloum, Maher N.; Shugard, Andrew D.; Kanouff, Michael P.; Gharagozloo, Patricia E.

    2013-03-01

    Modeling of reacting flows in porous media has become particularly important with the increased interest in hydrogen solid-storage beds. An advanced type of storage bed has been proposed that utilizes oxidation of uranium hydride to heat and decompose the hydride, releasing the hydrogen. To reduce the cost and time required to develop these systems experimentally, a valid computational model is required that simulates the reaction of uranium hydride and oxygen gas in a hydrogen storage bed using multiphysics finite element modeling. This SAND report discusses the advancements made in FY12 (since our last SAND report SAND2011-6939) to the model developed as a part of an ASC-P&EM project to address the shortcomings of the previous model. The model considers chemical reactions, heat transport, and mass transport within a hydride bed. Previously, the time-varying permeability and porosity were considered uniform. This led to discrepancies between the simulated results and experimental measurements. In this work, the effects of non-uniform changes in permeability and porosity due to phase and thermal expansion are accounted for. These expansions result in mechanical stresses that lead to bed deformation. To describe this, a simplified solid mechanics model for the local variation of permeability and porosity as a function of the local bed deformation is developed. By using this solid mechanics model, the agreement between our reacting bed model and the experimental data is improved. Additionally, more accurate uranium hydride oxidation kinetics parameters are obtained by fitting the experimental results from a pure uranium hydride oxidation measurement to the ones obtained from the coupled transport-solid mechanics model. Finally, the coupled transport-solid mechanics model governing equations and boundary conditions are summarized and recommendations are made for further development of ARIA and other Sandia codes in order for them to sufficiently implement the model.

  11. Evaluation of therapeutic effect of omega-6 linoleic acid and thymoquinone enriched extracts from Nigella sativa oil in the mitigation of lipidemic oxidative stress in rats.

    Science.gov (United States)

    Ahmad, Shafeeque; Beg, Zafarul H

    2016-06-01

    Nigella sativa belongs to the Ranunculaceae family. The therapeutic role of methanolic extract (ME) and volatile oil (VO) fractionated from N. sativa seed oil was investigated for antiperoxidative and antioxidant effects in atherogenic suspension fed rats. We examined the protective effects of ME and VO on the enzymatic and nonenzymatic antioxidants status in erythrocytes and the livers of atherogenic suspension fed rats. As a marker of lipid peroxidation, we estimated the conjugated diene, lipid hydroperoxide, and malondialdehyde concentrations in plasma in the following groups of rats: normolipidemic control, hyperlipidemic control, hyperlipidemic methanolic extract, and hyperlipidemic volatile oil. ME 500 mg or VO 100 mg/kg body weight of male rat was orally administrated for 30 d. Pretreatment of hyperlipidemic rats with these test extracts resulted in a significant decrease (P < 0.001) in the level of lipid peroxidation markers, conjugated diene, lipid hydroperoxide, and malondialdehyde (16-50%) compared to the hyperlipidemic control rats. In addition, ME and VO significantly (P < 0.001) elevated the hepatic and erythrocyte superoxide dismutase, catalase, and glutathione reductase activities (19-58%) compared to the hyperlipidemic rats. In liver homogenate of hyperlipidemic-ME and hyperlipidemic-VO, the glutathione-S-transferase activity was protected by 93% and 89%, and in erythrocytes, the glutathione peroxidase activity was protected by 90% and 77%, respectively. Interestingly, reduced glutathione level and activities of ATPases were protected to near normal levels. Pretreatment of rats with the test extracts replenished effectively (P < 0.001) the plasma total antioxidant power by an average of 88% against free radicals. The lipidemic oxidative stress was effectively mitigated by antiperoxidative activities of ME and VO. Thus, these test extracts, especially ME, may be used as antioxidant as well as hypolipidemic agents in the form of natural food

  12. Sensory Evaluation and Oxidative Stability of a Suncream Formulated with Thermal Spring Waters from Ourense (NW Spain and Sargassum muticum Extracts

    Directory of Open Access Journals (Sweden)

    Elena Balboa

    2017-06-01

    Full Text Available The purpose of this work was to evaluate four thermal spring waters from Ourense and a Sargassum muticum extract as cosmetic ingredients for the preparation of a suncream. The thermal spring waters were tested for their suitability as an aqueous phase main component, and the algal extract was added as an antioxidant instead of using synthetic preservatives in the cosmetic formula. The emulsion was tested for lipid oxidation during a period of 9 months and for consumer acceptance by performing a sensory test on controls and blanks. Further, color parameters were considered, and a pH determination was performed. The S. muticum extract protected from primary and secondary oxidation as efficiently as Fucus sp. or α-tocopherol extracts. In addition, the sensorial test revealed that consumers preferred suncreams prepared with the S. muticum extract and with thermal spring water from O Tinteiro and A Chavasqueira. The pH of the suncreams varied with the selection of the ingredients, and no oscillations in colorimetric values were visually observed. Our results indicate that the algal extract and the thermal spring waters from Ourense are potential cosmetic ingredients, since they showed effectiveness as antioxidant ingredients, and the suncreams were well accepted by consumers.

  13. Water-structuring technology with the molecular chaperone proteins: indicated application of the α-crystallin domains and imidazole-containing peptidomimetics in cosmetic skin care systems or dermatological therapeutic drug carrier formulations.

    Science.gov (United States)

    Babizhayev, Mark A; Nikolayev, Gennady M; Nikolayeva, Juliana G; Yegorov, Yegor E

    2011-01-01

    Changes in structural proteins and hydration during aging are responsible for altered skin morphologic and mechanical properties manifested as wrinkling, sagging, loss of elasticity, and apparent dryness. Impairment in protein hydration may add to the ultrastructural, mechanical, and biochemical changes in structural proteins in the aged skin. At Innovative Vision Products, Inc., we have pioneered a molecular chaperone protein-activated therapeutic or cosmetic platform to enable simultaneous analysis of water-binding and structuring characteristics for biology-related or skin aging and skin disease-related pathways. This cutting-edge technology has changed the hydration of proteins in photoaged skin which so that they are more compact and interact with water to limited degree. The mechanisms of skin diseases, aging, and cellular and signaling pathways mediated by targeting with molecular chaperone protein(s) are considered. Skin lesions that are growing, spreading, or pigmented, and those that occur on exposed areas of skin are likely to be treated by these emerging pharmacological chaperones that could have cosmetic or dermatological benefits. Examples of such chaperones are anti-/trans-glycation-imidazole-containing peptidomimetic(s) (natural L-carnosine derivatives and mimetics) combined with the molecular chaperone protein α-crystallin derived from a natural source, brine shrimp (Artemia franciscana) cysts, or with recombinant human αA-crystallin. This patented biotechnology represents an efficient tool with which to mitigate the consequences of free radical-induced skin damage. The article is organized to provide in one place all of the relevant technical information, such as high-performance nuclear magnetic resonance and electron spin resonance application tools, and to describe the entire process from sample preparation to data analysis, which is moving from biological studies to biotechnology batches of the product. The proposed biotechnology results in

  14. GEP-based method to formulate adhesion strength and hardness of Nb PVD coated on Ti-6Al-7Nb aimed at developing mixed oxide nanotubular arrays.

    Science.gov (United States)

    Rafieerad, A R; Bushroa, A R; Nasiri-Tabrizi, B; Fallahpour, A; Vadivelu, J; Musa, S N; Kaboli, S H A

    2016-08-01

    PVD process as a thin film coating method is highly applicable for both metallic and ceramic materials, which is faced with the necessity of choosing the correct parameters to achieve optimal results. In the present study, a GEP-based model for the first time was proposed as a safe and accurate method to predict the adhesion strength and hardness of the Nb PVD coated aimed at growing the mixed oxide nanotubular arrays on Ti67. Here, the training and testing analysis were executed for both adhesion strength and hardness. The optimum parameter combination for the scratch adhesion strength and micro hardness was determined by the maximum mean S/N ratio, which was 350W, 20 sccm, and a DC bias of 90V. Results showed that the values calculated in the training and testing in GEP model were very close to the actual experiments designed by Taguchi. The as-sputtered Nb coating with highest adhesion strength and microhardness was electrochemically anodized at 20V for 4h. From the FESEM images and EDS results of the annealed sample, a thick layer of bone-like apatite was formed on the sample surface after soaking in SBF for 10 days, which can be connected to the development of a highly ordered nanotube arrays. This novel approach provides an outline for the future design of nanostructured coatings for a wide range of applications. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Two and three way spectrophotometric-assisted multivariate determination of linezolid in the presence of its alkaline and oxidative degradation products and application to pharmaceutical formulation

    Science.gov (United States)

    Hegazy, Maha Abd El-Monem; Eissa, Maya Shaaban; Abd El-Sattar, Osama Ibrahim; Abd El-Kawy, Mohammad

    2014-07-01

    Linezolid (LIN) is determined in the presence of its alkaline (ALK) and oxidative (OXD) degradation products without preliminary separation based on ultraviolet spectrophotometry using two-way chemometric methods; principal component regression (PCR) and partial least-squares (PLS), and three-way chemometric methods; parallel factor analysis (PARAFAC) and multi-way partial least squares (N-PLS). A training set of mixtures containing LIN, ALK and OXD; was prepared in the concentration ranges of 12-18, 2.4-3.6 and 1.2-1.8 μg mL-1, respectively according to a multilevel multifactor experimental design. The multivariate calibrations were obtained by measuring the zero-order absorbance from 220 to 320 nm using the training set. The validation of the multivariate methods was realized by analyzing their synthetic mixtures. The capabilities of the chemometric analysis methods for the analysis of real samples were evaluated by determination of LIN in its pharmaceutical preparation with satisfactory results. The accuracy of the methods, evaluated through the root mean square error of prediction (RMSEP), was 0.058, 0.026, 0.101 and 0.026 for LIN using PCR, PLS, PARAFAC and N-PLS, respectively. Protolytic equilibria of LIN and its degradation products were evaluated using the corresponding absorption spectra-pH data obtained with PARAFAC. The obtained pKa values of LIN, ALK and OXD are 5.70, 8.90 and 6.15, respectively. The results obtained were statistically compared to that of a reported HPLC method, and there was no significant difference between the proposed methods and the reported method regarding both accuracy and precision.

  16. Eco-Friendly Formulated Zinc Oxide Nanoparticles: Induction of Cell Cycle Arrest and Apoptosis in the MCF-7 Cancer Cell Line.

    Science.gov (United States)

    Boroumand Moghaddam, Amin; Moniri, Mona; Azizi, Susan; Abdul Rahim, Raha; Bin Ariff, Arbakariya; Navaderi, Mohammad; Mohamad, Rosfarizan

    2017-10-20

    Green products have strong potential in the discovery and development of unique drugs. Zinc oxide nanoparticles (ZnO NPs) have been observed to have powerful cytotoxicity against cells that cause breast cancer. The present study aims to examine the cell cycle profile, status of cell death, and pathways of apoptosis in breast cancer cells (MCF-7) treated with biosynthesized ZnO NPs. The anti-proliferative activity of ZnO NPs was determined using MTT assay. Cell cycle analysis and the mode of cell death were evaluated using a flow cytometry instrument. Quantitative real-time-PCR (qRT-PCR) was employed to investigate the expression of apoptosis in MCF-7 cells. ZnO NPs were cytotoxic to the MCF-7 cells in a dose-dependent manner. The 50% growth inhibition concentration (IC 50 ) of ZnO NPs at 24 h was 121 µg/mL. Cell cycle analysis revealed that ZnO NPs induced sub-G₁ phase (apoptosis), with values of 1.87% at 0 μg/mL (control), 71.49% at IC 25 , 98.91% at IC 50 , and 99.44% at IC 75 . Annexin V/propidium iodide (PI) flow cytometry analysis confirmed that ZnO NPs induce apoptosis in MCF-7 cells. The pro-apoptotic genes p53 , p21 , Bax , and JNK were upregulated, whereas anti-apoptotic genes Bcl-2 , AKT1 , and ERK1/2 were downregulated in a dose-dependent manner. The arrest and apoptosis of MCF-7 cells were induced by ZnO NPs through several signalling pathways.

  17. The Protective and Therapeutic Roles of Hexamethylenetetramine and N-Acetyl-Cysteine on Sulfur Mustard-Induced Oxidative Stress in Rat Serum

    Directory of Open Access Journals (Sweden)

    M Jafari

    2016-04-01

    Conclusion: The study findings revealed that SM induces oxidative stress in rat serum. HMT and NAC can ameliorate SM-induced oxidative stress by altering antioxidant defense system in serum. The protective effect of HMT against the toxicity of SM is higher than NAC.

  18. Drug Nanoparticle Formulation Using Ascorbic Acid Derivatives

    Directory of Open Access Journals (Sweden)

    Kunikazu Moribe

    2011-01-01

    Full Text Available Drug nanoparticle formulation using ascorbic acid derivatives and its therapeutic uses have recently been introduced. Hydrophilic ascorbic acid derivatives such as ascorbyl glycoside have been used not only as antioxidants but also as food and pharmaceutical excipients. In addition to drug solubilization, drug nanoparticle formation was observed using ascorbyl glycoside. Hydrophobic ascorbic acid derivatives such as ascorbyl mono- and di-n-alkyl fatty acid derivatives are used either as drugs or carrier components. Ascorbyl n-alkyl fatty acid derivatives have been formulated as antioxidants or anticancer drugs for nanoparticle formulations such as micelles, microemulsions, and liposomes. ASC-P vesicles called aspasomes are submicron-sized particles that can encapsulate hydrophilic drugs. Several transdermal and injectable formulations of ascorbyl n-alkyl fatty acid derivatives were used, including ascorbyl palmitate.

  19. Macromolecular therapeutics.

    Science.gov (United States)

    Yang, Jiyuan; Kopeček, Jindřich

    2014-09-28

    This review covers water-soluble polymer-drug conjugates and macromolecules that possess biological activity without attached low molecular weight drugs. The main design principles of traditional and backbone degradable polymer-drug conjugates as well as the development of a new paradigm in nanomedicines - (low molecular weight) drug-free macromolecular therapeutics are discussed. To address the biological features of cancer, macromolecular therapeutics directed to stem/progenitor cells and the tumor microenvironment are deliberated. Finally, the future perspectives of the field are briefly debated. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. 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.

  1. Formulation, development and evaluation of colon-specific ketorolac ...

    African Journals Online (AJOL)

    The major intention to formulate and develop colon targeted tablets is to improve the therapeutic efficacy by increasing therapeutic drug concentrations in colon. The present study was aimed to develop guar gum compression coated tablets ketorolac tromethamine to achieve the colon-specific drug release. In this study ...

  2. Novel self-nanoemulsifying formulation of quercetin

    DEFF Research Database (Denmark)

    Jain, Amit K; Thanki, Kaushik; Jain, Sanyog

    2014-01-01

    . This appreciation was further supported by normalized levels of tumor angiogenesis markers (MMP-2, MMP-9, TNF-α and IL-6). At higher doses (100mg/kg) the pro-oxidant activity was noted and exhibited significantly higher therapeutic anticancer efficacy (~65% tumor suppression) in the same model as compared...... significantly higher therapeutic anticancer efficacy (~65% tumor suppression) was noted in the same model as compared to that of free quercetin (~20%)....

  3. Audits of radiopharmaceutical formulations

    International Nuclear Information System (INIS)

    Castronovo, F.P. Jr.

    1992-01-01

    A procedure for auditing radiopharmaceutical formulations is described. To meet FDA guidelines regarding the quality of radiopharmaceuticals, institutional radioactive drug research committees perform audits when such drugs are formulated away from an institutional pharmacy. All principal investigators who formulate drugs outside institutional pharmacies must pass these audits before they can obtain a radiopharmaceutical investigation permit. The audit team meets with the individual who performs the formulation at the site of drug preparation to verify that drug formulations meet identity, strength, quality, and purity standards; are uniform and reproducible; and are sterile and pyrogen free. This team must contain an expert knowledgeable in the preparation of radioactive drugs; a radiopharmacist is the most qualified person for this role. Problems that have been identified by audits include lack of sterility and apyrogenicity testing, formulations that are open to the laboratory environment, failure to use pharmaceutical-grade chemicals, inadequate quality control methods or records, inadequate training of the person preparing the drug, and improper unit dose preparation. Investigational radiopharmaceutical formulations, including nonradiolabeled drugs, must be audited before they are administered to humans. A properly trained pharmacist should be a member of the audit team

  4. Reactive decontamination formulation

    Science.gov (United States)

    Giletto, Anthony [College Station, TX; White, William [College Station, TX; Cisar, Alan J [Cypress, TX; Hitchens, G Duncan [Bryan, TX; Fyffe, James [Bryan, TX

    2003-05-27

    The present invention provides a universal decontamination formulation and method for detoxifying chemical warfare agents (CWA's) and biological warfare agents (BWA's) without producing any toxic by-products, as well as, decontaminating surfaces that have come into contact with these agents. The formulation includes a sorbent material or gel, a peroxide source, a peroxide activator, and a compound containing a mixture of KHSO.sub.5, KHSO.sub.4 and K.sub.2 SO.sub.4. The formulation is self-decontaminating and once dried can easily be wiped from the surface being decontaminated. A method for decontaminating a surface exposed to chemical or biological agents is also disclosed.

  5. Nanoscale science and engineering forum (706c) design of solid lipid particles with iron oxide quantum dots for the delivery of therapeutic agents

    Science.gov (United States)

    Solid lipid particles provide a method to encapsulate and control the release of drugs in vivo but lack the imaging capability provided by CdS quantum dots. This shortcoming was addressed by combining these two technologies into a model system that uses iron oxide as a non-toxic imaging component in...

  6. Preparation of radiopharmaceutical formulations

    International Nuclear Information System (INIS)

    Simon, J.; Garlich, J.R.; Frank, R.K.; McMillan, K.

    1998-01-01

    Radiopharmaceutical formulations for complexes comprising at least one radionuclide complexed with a ligand, or its physiologically-acceptable salts thereof, especially 153 samarium-ethylenediaminetetramethylenephosphonic acid, which optionally contains a divalent metal ion, e.g. calcium, and is frozen, thawed, and then administered by injection. Alternatively, the radiopharmaceutical formulations must contain the divalent metal and are frozen only if the time before administration is sufficiently long to cause concern for radiolysis of the ligand. 2 figs., 9 tabs

  7. Tariff formulation and equalization

    International Nuclear Information System (INIS)

    Svartsund, Trond

    2003-01-01

    The primary goal of the transmission tariff is to provide for socioeconomic use of the transmission grid. The present tariff structure is basically right. The responsibility for the formulation of the tariff resides with the local grid owner. This must take place in agreement with the current regulations which are passed by the authorities. The formulation must be adaptable to the local requirements. EBL (Norwegian Electricity Industry Association) is content with the current regulations

  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. Therapeutic effect of aqueous extracts of three dietary spices and their mixture on lipid metabolism and oxidative stress in a rat model of chronic alcohol consumption.

    Science.gov (United States)

    Otunola, Gloria Aderonke; Afolayan, Anthony Jide

    2016-07-01

    The protective effect of aqueous extracts of three dietary spices, garlic, (Allium sativum), ginger (Zingiber officinale) and pepper (Capsicum frutescens) singly and combined was investigated using a rat model of chronic alcohol intake. Rats were given 30% ethanol, with or without aqueous extracts of garlic, ginger, pepper or mixture of the three administered at 200mg/kg body weight by oral gavage for 28 days. Lipid profile, lipid peroxidation, oxidative and antioxidative profiles of serum, faecal, liver, kidney, heart and brain tissues of the rats were analyzed. Alcohol treatment significantly elevated liver enzymes, lipid peroxidation, depleted antioxidant system and induced histopathological changes in the liver. These alterations were markedly ameliorated by treatment with aqueous extracts of the three spices singly or mixed at 200mg/kg body weight. These results suggest that aqueous extracts of garlic, ginger, pepper or a blend of the three protects against alcohol- induced hypercholesterolemia, lipid peroxidation, oxidative stress and liver damage.

  10. Granulated decontamination formulations

    Science.gov (United States)

    Tucker, Mark D.

    2007-10-02

    A decontamination formulation and method of making that neutralizes the adverse health effects of both chemical and biological compounds, especially chemical warfare (CW) and biological warfare (BW) agents, and toxic industrial chemicals. The formulation provides solubilizing compounds that serve to effectively render the chemical and biological compounds, particularly CW and BW compounds, susceptible to attack, and at least one reactive compound that serves to attack (and detoxify or kill) the compound. The formulation includes at least one solubilizing agent, a reactive compound, a sorbent additive, and water. A highly adsorbent sorbent additive (e.g., amorphous silica, sorbitol, mannitol, etc.) is used to "dry out" one or more liquid ingredients into a dry, free-flowing powder that has an extended shelf life, and is more convenient to handle and mix in the field.

  11. High-Level Waste Glass Formulation Model Sensitivity Study 2009 Glass Formulation Model Versus 1996 Glass Formulation Model

    International Nuclear Information System (INIS)

    Belsher, J.D.; Meinert, F.L.

    2009-01-01

    This document presents the differences between two HLW glass formulation models (GFM): The 1996 GFM and 2009 GFM. A glass formulation model is a collection of glass property correlations and associated limits, as well as model validity and solubility constraints; it uses the pretreated HLW feed composition to predict the amount and composition of glass forming additives necessary to produce acceptable HLW glass. The 2009 GFM presented in this report was constructed as a nonlinear optimization calculation based on updated glass property data and solubility limits described in PNNL-18501 (2009). Key mission drivers such as the total mass of HLW glass and waste oxide loading are compared between the two glass formulation models. In addition, a sensitivity study was performed within the 2009 GFM to determine the effect of relaxing various constraints on the predicted mass of the HLW glass.

  12. New therapeutic activity of metabolic enhancer piracetam in treatment of neurodegenerative disease: Participation of caspase independent death factors, oxidative stress, inflammatory responses and apoptosis.

    Science.gov (United States)

    Verma, Dinesh Kumar; Gupta, Sonam; Biswas, Joyshree; Joshi, Neeraj; Singh, Abhishek; Gupta, Parul; Tiwari, Shubhangini; Sivarama Raju, K; Chaturvedi, Swati; Wahajuddin, M; Singh, Sarika

    2018-03-16

    Piracetam, a nootropic drug that has been clinically used for decades but remains enigmatic due to no distinct understanding of its mechanism of action. The present study aimed to investigate the role of caspase independent pathway in piracetam mediated neuroprotection. LPS administration caused significant alterations in oxidative stress related parameters like glutathione, glutathione reductase and increased lipid peroxidation. LPS administration also caused augmented expression of inflammatory cytokines and astrocytes activation. Piracetam treatment offered significant protection against LPS induced oxidative and inflammatory parameters and inhibited astrocytes activation. LPS administration caused augmented level of reactive oxygen species and depleted mitochondrial membrane potential which were attenuated with piracetam treatment. This study for the first time demonstrates the role of caspase independent death factors in piracetam induced neuroprotective effects in rat brain. Translocation of mitochondrial resident apoptosis inducing factor and endonuclease G to nucleus through cytosol after LPS administration was significantly blocked with piracetam treatment. Further, LPS induced DNA fragmentation along with up regulated Poly [ADP-ribose] polymerase 1 (PARP1) levels were also inhibited with piracetam treatment. Apoptotic death was confirmed by the cleavage of caspase 3 as well as histological alteration in rat brain regions. LPS administration caused significantly increased level of cleaved caspase 3, altered neuronal morphology and decreased neuronal density which were restored with piracetam treatment. Collectively our findings indicate that piracetam offered protection against LPS induced inflammatory responses and cellular death including its antioxidative antiapoptotic activity with its attenuation against mitochondria mediated caspase independent pathway. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Therapeutics role of olive fruits/oil in the prevention of diseases via modulation of anti-oxidant, anti-tumour and genetic activity.

    Science.gov (United States)

    Rahmani, Arshad H; Albutti, Aqel S; Aly, Salah M

    2014-01-01

    The current mode of treatment for various diseases is based on synthetic drugs are effective but they show adverse effect and also alter the genetic and metabolic activity. Moreover, some drugs prepared from plants and their constituents show potentiality with more efficacy than synthetic agents used in clinical therapy. Earlier report has shown that regular consumption of fruits and vegetables is strongly related with reduced risk of developing various diseases. Several epidemiological studies has shown that, the incidence heart disease and cancers is lowest in the Mediterranean basin as compared to the part of the world because of their diet rich in olives and olive products. Olives are commonly consumed in Mediterranean and Arabian Peninsula and also have been documented in Holy Quran and modern scientific literatures. Earlier studies have shown that, the constituents from olive such as oleuropein, squalene and hydroxytyrosol modulate the genes functions and other activities. In this review, the medicinal value of olives and their constituents are summarized in terms of therapeutic approach in the diseases management through regulation of various activities.

  14. Radiation treatment of combustion gases: formulation and test of a reaction model

    International Nuclear Information System (INIS)

    Busi, F.; D'Angelantonio, M.; Mulazzani, Q.G.; Raffaelli, V.; Tubertini, O.

    1985-01-01

    A generalized kinetic mechanism for radiation induced oxidation of nitrogen oxides from exhaust gases in the absence of sulfur dioxide is formulated. The responses obtained by the mathematical simulation are in good agreement with reported experimental results. (author)

  15. Screening vaccine formulations for biological activity using fresh human whole blood.

    OpenAIRE

    Brookes, RH; Hakimi, J; Ha, Y; Aboutorabian, S; Ausar, SF; Hasija, M; Smith, SG; Todryk, SM; Dockrell, HM; Rahman, N

    2014-01-01

    Understanding the relevant biological activity of any pharmaceutical formulation destined for human use is crucial. For vaccine-based formulations, activity must reflect the expected immune response, while for non-vaccine therapeutic agents, such as monoclonal antibodies, a lack of immune response to the formulation is desired. During early formulation development, various biochemical and biophysical characteristics can be monitored in a high-throughput screening (HTS) format. However, it rem...

  16. The Involvement of Arginase and Nitric Oxide Synthase in Breast Cancer Development: Arginase and NO Synthase as Therapeutic Targets in Cancer

    Directory of Open Access Journals (Sweden)

    Nikolay Avtandilyan

    2018-01-01

    Full Text Available It is well established that, during development of malignancies, metabolic changes occur, including alterations of enzyme activities and isoenzyme expression. Arginase and nitric oxide (NO synthase (NOS are two of those enzymes considered to be involved in tumorigenesis. The goal of this article was to study the involvement of arginase and NOS in the development of different stages of breast cancer. Our results have shown that human serum arginase activity and NO (resp., and NOS activity and polyamines quantities increased in parallel with cancer stage progression and decreased after neoadjuvant chemotherapy. For breast cancer, the only isoenzyme of arginase expressed in serum before and after chemotherapy was in a cationic form. The data of Lineweaver-Burk plot with a Km value of 2 mM was calculated, which is characteristic for human liver type isoform of arginase. During electrophoresis at pH 8.9, the enzyme exhibited high electrophoretic mobility and was detected near the anode. The presented results demonstrated that arginase in human serum with breast cancer and after chemotherapy is not polymorphic. We suggest that arginase and NOS inhibition has antitumor effects on cancer development, as it can inhibit polyamines and NO levels, a precursor of cancer cell proliferation, metastasis, and tumor angiogenesis.

  17. DNA/RNA-based formulations for treatment of breast cancer.

    Science.gov (United States)

    Xie, Zhaolu; Zeng, Xianghui

    2017-12-01

    To develop a successful formulation for the gene therapy of breast cancer, an effective therapeutic nucleic acid and a proper delivery system are essential. Increased understanding of breast cancer, and developments in biotechnology, material science and nanotechnology have provided a major impetus in the development of effective formulations for the gene therapy of breast cancer. Areas covered: We discuss DNA/RNA-based formulations that can inhibit the growth of breast cancer cells and control the progress of breast cancer. Targets for the gene therapy of breast cancer, DNA/RNA-based therapeutics and delivery systems are summarized. And examples of successful DNA/RNA-based formulations for breast cancer gene therapy are reviewed. Expert opinion: Several challenges remain in developing effective DNA/RNA-based formulations for treatment of breast cancer. Firstly, most of the currently utilized targets are not effective enough as monotherapy for breast cancer. Secondly, the requirements for co-delivery system make the preparation of formulation more complicated. Thirdly, nanoparticles with the modification of tumor-targeting ligands could be more unstable in circulation and normal tissues. Lastly, immune responses against the viral vectors are unfavorable for the gene therapy of breast cancer because of the damage to the host and the impaired therapeutic ability.

  18. Role reductants in dilute chemical decontamination formulations

    Energy Technology Data Exchange (ETDEWEB)

    Ranganathan, S. [Univ. of New Brunswick (Canada). Dept. of Chemical Engineering; Srinivasan, M.P.; Narasimhan, S.V. [Bhabha Atomic Research Centre (BARC), Trombay, Mumbai (India). Water and Steam Chemistry Lab.; Raghavan, P.S. [Madras Christian Coll., Chennai (India); Gopalan, R. [Madras Christian Coll., Chennai (India). Dept. of Chemistry

    2004-10-01

    Iron(III) oxides are the major corrosion products formed in boiling water reactors. The iron(III) oxides are of two types, namely hematite ({alpha}-Fe{sub 2}O{sub 3}) and maghemite ({gamma}-Fe{sub 2}O{sub 3}). The dissolution of these oxides is in no way simple because of the labile nature of the Fe(III)-O bond towards the chelants. The leaching of metal ions is partially controlled by reductive dissolution. In order to understand the role of the reductant, it is essential to study the dissolution behaviour of a system like Fe{sub 2}O{sub 3}, which does not contain any Fe{sup 2+} in the crystal lattice. The present study was carried out with {gamma}-Fe{sub 2}O{sub 3} and dilute chemical decontamination (DCD) formulations containing ascorbic acid and citric acid with the addition of Fe(II)-L as a reductant. The chelants used for the dissolution process were nitrilotriacetic acid, 2,6-pyridinedicorboxylic acid and ethylenediaminetetraacetic acid. The {gamma}-Fe{sub 2}O{sub 3} was chosen since the earlier studies revealed that the dissolution kinetics of {alpha}-Fe{sub 2}O{sub 3} is slow and it is difficult to dissolve even by strong complexing agents, whereas {gamma}-Fe{sub 2}O{sub 3} dissolution is comparatively easier. This is due to the structural difference between these two oxides. The studies also revealed that the dissolution was partly influenced by the nature of the chelating agents but mainly controlled by the power of the reductants used in the formulation. The dissolution behaviour of {gamma}-Fe{sub 2}O{sub 3} under various experimental conditions is discussed and compared with that of magnetite in order to arrive at a suitable mechanism for the dissolution of iron oxides and emphasize the role of reductants in DCD formulations. (orig.)

  19. Recent progress in nanomedicine: therapeutic, diagnostic and theranostic applications

    NARCIS (Netherlands)

    Rizzo, L.Y.; Theek, B.; Storm, Gerrit; Kiessling, F.; Lammers, Twan Gerardus Gertudis Maria

    2013-01-01

    In recent years, the use of nanomedicine formulations for therapeutic and diagnostic applications has increased exponentially. Many different systems and strategies have been developed for drug targeting to pathological sites, as well as for visualizing and quantifying important (patho-)

  20. Role of gut microbiota and oxidative stress in the progression of non-alcoholic fatty liver disease to hepatocarcinoma: Current and innovative therapeutic approaches

    Directory of Open Access Journals (Sweden)

    Antonella Borrelli

    2018-05-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD represents the most common chronic liver disease in industrialized countries. NAFLD progresses through the inflammatory phase of non-alcoholic steatohepatitis (NASH to fibrosis and cirrhosis, with some cases developing liver failure or hepatocellular carcinoma (HCC. Liver biopsy remains the gold standard approach to a definitive diagnosis of NAFLD and the distinction between simple steatosis and NASH. The pathogenesis of NASH is still not clear. Several theories have been proposed ranging from the “Two Hit Theory” to the “Multiple Hit Theory”. However, the general consensus is that the gut microbiota, oxidative stress, and mitochondrial damage play key roles in the pathogenesis of NASH. The interaction between the gut epithelia and some commensal bacteria induces the rapid generation of reactive oxygen species (ROS. The main goal of any therapy addressing NASH is to reverse or prevent progression to liver fibrosis/cirrhosis. This problem represents the first “Achilles’ heel” of the new molecules being evaluated in most ongoing clinical trials. The second is the inability of these molecules to reach the mitochondria, the primary sites of energy production and ROS generation. Recently, a variety of non-pharmacological and pharmacological treatment approaches for NASH have been evaluated including vitamin E, the thiazolidinediones, and novel molecules related to NASH pathogenesis (including obeticholic acid and elafibranor. Recently, a new isoform of human manganese superoxide dismutase (MnSOD was isolated and obtained in a synthetic recombinant form designated rMnSOD. This protein has been shown to be a powerful antioxidant capable of mediating ROS dismutation, penetrating biological barriers via its uncleaved leader peptide, and reducing portal hypertension and fibrosis in rats affected by liver cirrhosis. Based on these distinctive characteristics, it can be hypothesized that this novel

  1. RAACFDb: Rheumatoid arthritis ayurvedic classical formulations database.

    Science.gov (United States)

    Mohamed Thoufic Ali, A M; Agrawal, Aakash; Sajitha Lulu, S; Mohana Priya, A; Vino, S

    2017-02-02

    In the past years, the treatment of rheumatoid arthritis (RA) has undergone remarkable changes in all therapeutic modes. The present newfangled care in clinical research is to determine and to pick a new track for better treatment options for RA. Recent ethnopharmacological investigations revealed that traditional herbal remedies are the most preferred modality of complementary and alternative medicine (CAM). However, several ayurvedic modes of treatments and formulations for RA are not much studied and documented from Indian traditional system of medicine. Therefore, this directed us to develop an integrated database, RAACFDb (acronym: Rheumatoid Arthritis Ayurvedic Classical Formulations Database) by consolidating data from the repository of Vedic Samhita - The Ayurveda to retrieve the available formulations information easily. Literature data was gathered using several search engines and from ayurvedic practitioners for loading information in the database. In order to represent the collected information about classical ayurvedic formulations, an integrated database is constructed and implemented on a MySQL and PHP back-end. The database is supported by describing all the ayurvedic classical formulations for the treatment rheumatoid arthritis. It includes composition, usage, plant parts used, active ingredients present in the composition and their structures. The prime objective is to locate ayurvedic formulations proven to be quite successful and highly effective among the patients with reduced side effects. The database (freely available at www.beta.vit.ac.in/raacfdb/index.html) hopefully enables easy access for clinical researchers and students to discover novel leads with reduced side effects. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. 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.

  3. 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.

  4. Systematic Equation Formulation

    DEFF Research Database (Denmark)

    Lindberg, Erik

    2007-01-01

    A tutorial giving a very simple introduction to the set-up of the equations used as a model for an electrical/electronic circuit. The aim is to find a method which is as simple and general as possible with respect to implementation in a computer program. The “Modified Nodal Approach”, MNA, and th......, and the “Controlled Source Approach”, CSA, for systematic equation formulation are investigated. It is suggested that the kernel of the P Spice program based on MNA is reprogrammed....

  5. Drug delivery and formulations.

    Science.gov (United States)

    Breitkreutz, Jörg; Boos, Joachim

    2011-01-01

    Paediatric drug delivery is a major challenge in drug development. Because of the heterogeneous nature of the patient group, ranging from newborns to adolescents, there is a need to use appropriate excipients, drug dosage forms and delivery devices for different age groups. So far, there is a lack of suitable and safe drug formulations for children, especially for the very young and seriously ill patients. The new EU legislation will enforce paediatric clinical trials and drug development. Current advances in paediatric drug delivery include interesting new concepts such as fast-dissolving drug formulations, including orodispersible tablets and oral thin strips (buccal wafers), and multiparticulate dosage forms based on mini-tabletting or pelletization technologies. Parenteral administration is likely to remain the first choice for children in the neonatal period and for emergency cases. Alternative routes of administration include transdermal, pulmonary and nasal drug delivery systems. A few products are already available on the market, but others still need further investigations and clinical proof of concept.

  6. Ether formulations of relativity

    International Nuclear Information System (INIS)

    Duffy, M.C.

    1980-01-01

    Contemporary ether theories are surveyed and criticised, especially those formally identical to orthodox Relativity. The historical development of Relativity, Special and General, in terms of an ether, is briefly indicated. Classical interpretations of Generalized Relativity using ether are compared to Euclidean formulations using a background space. The history of a sub-group of theories, formulating a 'new' Relativity involving modified transforms, is outlined. According to the theory with which they agree, recent supposed detections of drift are classified and criticised. Cosmological evidence suggesting an ether is mentioned. Only ether theories formally identical to Relativity have been published in depth. They stand criticised as being contrary to the positivist spirit. The history of mechanical analogues is traced, from Hartley's representing gravitating matter as spherical standing waves, to recent suggestions that vortex-sponge might model electromagnetic, quantum, uncertainty and faster-than-light phenomena. Contemporary theories are particular physical theories, themselves 'second interpretations' of a primary mathematical model. Mechanical analogues are auxiliary, not necessary, to other theory, disclosing relationships between classical and non-classical descriptions of assemblies charging state. The ether-relativity polemic, part of a broader dispute about relativity, is founded on mistaken conceptions of the roles of mathematical and physical models, mechanical analogues; and a distored view of history, which indicates that ether theories have become relativistic. (author)

  7. Reactive formulations for a neutralization of toxic industrial chemicals

    Science.gov (United States)

    Tucker, Mark D [Albuqueruqe, NM; Betty, Rita G [Rio Rancho, NM

    2006-10-24

    Decontamination formulations for neutralization of toxic industrial chemicals, and methods of making and using same. The formulations are effective for neutralizing malathion, hydrogen cyanide, sodium cyanide, butyl isocyanate, carbon disulfide, phosgene gas, capsaicin in commercial pepper spray, chlorine gas, anhydrous ammonia gas; and may be effective at neutralizing hydrogen sulfide, sulfur dioxide, formaldehyde, ethylene oxide, methyl bromide, boron trichloride, fluorine, tetraethyl pyrophosphate, phosphorous trichloride, arsine, and tungsten hexafluoride.

  8. Vozy formule 1

    OpenAIRE

    Zbožínek, Adam

    2009-01-01

    Tato práce uvádí základní pravidla a předpoklady pro konstrukci a použití vozů formule 1. Hlavní zaměření je na aerodynamiku, která je nejdůležitější disciplínou v tomto motoristickém sportu, dále je tato práce zaměřena na základní faktory týkající se motoru vozu, kol, nové technologie KERS a provedení volantu. This work shows basic rules and conditions for construction and use of cars formula 1. The main part of this work focus on the aerodynamics which is the most important discipline of...

  9. Assessment of strategy formulation

    DEFF Research Database (Denmark)

    Acur, Nuran; Englyst, Linda

    2006-01-01

    of the success criteria through face-to-face interviews with 46 managers, workshops involving 40 managers, and two in-depth case studies. The success criteria have been slightly modified due to the empirical results, to yield the assessment tool. Findings – The resulting assessment tool integrates three generic...... approaches to strategy assessment, namely the goal-centred, comparative and improvement approaches, as found in the literature. Furthermore, it encompasses three phases of strategy formulation processes: strategic thinking, strategic planning and embedding of strategy. The tool reflects that the different......, but cases and managerial perceptions indicate that the need for accurate and detailed plans might be overrated in the literature, as implementation relies heavily on continuous improvement and empowerment. Concerning embedding, key aspects relate both to the goal-centred and improvement approaches, while...

  10. Development of polyherbal antidiabetic formulation encapsulated in the phospholipids vesicle system

    Directory of Open Access Journals (Sweden)

    Vinod Kumar Gauttam

    2013-01-01

    Full Text Available Multifactorial metabolic diseases, for instance diabetes develop several complications like hyperlipidemia, hepatic toxicity, immunodeficiency etc., Hence, instead of mono-drug therapy the management of the disease requires the combination of herbs. Marketed herbal drugs comprise of irrational combinations, which makes their quality control more difficult. Phytoconstituents, despite having excellent bioactivity in vitro demonstrate less or no in vivo actions due to their poor lipid solubility, resulting in high therapeutic dose regimen; phospholipids encapsulation can overcome this problem. Hence, present study was designed to develop a phospholipids encapsulated polyherbal anti-diabetic formulation. In the present study, polyherbal formulation comprises of lyophilized hydro-alcoholic (50% v/v extracts of Momordica charantia, Trigonella foenum-graecum and Withania somnifera 2:2:1, respectively, named HA, optimized based on oral glucose tolerance test model in normal Wistar rats. The optimized formulation (HA entrapped in the phosphatidylcholine and cholesterol (8:2 vesicle system is named HA lipids (HAL. The vesicles were characterized for shape, morphology, entrapment efficiency, polar-dispersity index and release profile in the gastric pH. The antidiabetic potential of HA, marketed polyherbal formulation (D-fit and HAL was compared in streptozotocin-induced diabetic rat model of 21 days study. The parameters evaluated were behavioral changes, body weight, serum glucose level, lipid profile and oxidative stress. The antidiabetic potential of HA (1000 mg/kg was at par with the D-fit (1000 mg/kg. However, the potential was enhanced by phospholipids encapsulation; as HAL (500 mg/kg has shown more significant (P < 0.05 potential in comparison to HA (1000 mg/kg and at par with metformin (500 mg/kg.

  11. Actinic radiation-curable formulations from the reaction product of organic isocyanate, poly(alkylene oxide) polyol and an unsaturated addition-polymerizable monomeric compound having a single isocyanate-reactive hydrogen group

    International Nuclear Information System (INIS)

    Howard, D.D.

    1979-01-01

    Energy-curable compositions which can be cured in the presence of air by exposure to actinic radiation contain at least one unsaturated urethane oligomer. The oligomer comprises the reaction product of at least one poly(alkylene oxide) polyol, at least one polyisocyanate, and at least one unsaturated active hydrogen-containing compound

  12. Macrophages offer a paradigm switch for CNS delivery of therapeutic proteins.

    Science.gov (United States)

    Klyachko, Natalia L; Haney, Matthew J; Zhao, Yuling; Manickam, Devika S; Mahajan, Vivek; Suresh, Poornima; Hingtgen, Shawn D; Mosley, R Lee; Gendelman, Howard E; Kabanov, Alexander V; Batrakova, Elena V

    2014-07-01

    Active targeted transport of the nanoformulated redox enzyme, catalase, in macrophages attenuates oxidative stress and as such increases survival of dopaminergic neurons in animal models of Parkinson's disease. Optimization of the drug formulation is crucial for the successful delivery in living cells. We demonstrated earlier that packaging of catalase into a polyion complex micelle ('nanozyme') with a synthetic polyelectrolyte block copolymer protected the enzyme against degradation in macrophages and improved therapeutic outcomes. We now report the manufacture of nanozymes with superior structure and therapeutic indices. Synthesis, characterization and therapeutic efficacy of optimal cell-based nanoformulations are evaluated. A formulation design for drug carriers typically works to avoid entrapment in monocytes and macrophages focusing on small-sized nanoparticles with a polyethylene glycol corona (to provide a stealth effect). By contrast, the best nanozymes for delivery in macrophages reported in this study have a relatively large size (≈ 200 nm), which resulted in improved loading capacity and release from macrophages. Furthermore, the cross-linking of nanozymes with the excess of a nonbiodegradable linker ensured their low cytotoxicity, and efficient catalase protection in cell carriers. Finally, the 'alternatively activated' macrophage phenotype (M2) utilized in these studies did not promote further inflammation in the brain, resulting in a subtle but statistically significant effect on neuronal regeneration and repair in vivo. The optimized cross-linked nanozyme loaded into macrophages reduced neuroinflammatory responses and increased neuronal survival in mice. Importantly, the approach for nanoformulation design for cell-mediated delivery is different from the common requirements for injectable formulations.

  13. Macrophages offer a paradigm switch for CNS delivery of therapeutic proteins

    Science.gov (United States)

    Klyachko, Natalia L; Haney, Matthew J; Zhao, Yuling; Manickam, Devika S; Mahajan, Vivek; Suresh, Poornima; Hingtgen, Shawn D; Mosley, R Lee; Gendelman, Howard E; Kabanov, Alexander V; Batrakova, Elena V

    2013-01-01

    Aims Active targeted transport of the nanoformulated redox enzyme, catalase, in macrophages attenuates oxidative stress and as such increases survival of dopaminergic neurons in animal models of Parkinson’s disease. Optimization of the drug formulation is crucial for the successful delivery in living cells. We demonstrated earlier that packaging of catalase into a polyion complex micelle (‘nanozyme’) with a synthetic polyelectrolyte block copolymer protected the enzyme against degradation in macrophages and improved therapeutic outcomes. We now report the manufacture of nanozymes with superior structure and therapeutic indices. Methods Synthesis, characterization and therapeutic efficacy of optimal cell-based nanoformulations are evaluated. Results A formulation design for drug carriers typically works to avoid entrapment in monocytes and macrophages focusing on small-sized nanoparticles with a polyethylene glycol corona (to provide a stealth effect). By contrast, the best nanozymes for delivery in macrophages reported in this study have a relatively large size (~200 nm), which resulted in improved loading capacity and release from macrophages. Furthermore, the cross-linking of nanozymes with the excess of a nonbiodegradable linker ensured their low cytotoxicity, and efficient catalase protection in cell carriers. Finally, the ‘alternatively activated’ macrophage phenotype (M2) utilized in these studies did not promote further inflammation in the brain, resulting in a subtle but statistically significant effect on neuronal regeneration and repair in vivo. Conclusion The optimized cross-linked nanozyme loaded into macrophages reduced neuroinflammatory responses and increased neuronal survival in mice. Importantly, the approach for nanoformulation design for cell-mediated delivery is different from the common requirements for injectable formulations. PMID:24237263

  14. Extensive preclinical investigation of polymersomal formulation of doxorubicin versus Doxil-mimic formulation.

    Science.gov (United States)

    Alibolandi, Mona; Abnous, Khalil; Mohammadi, Marzieh; Hadizadeh, Farzin; Sadeghi, Fatemeh; Taghavi, Sahar; Jaafari, Mahmoud Reza; Ramezani, Mohammad

    2017-10-28

    Due to the severe cardiotoxicity of doxorubicin, its usage is limited. This shortcoming could be overcome by modifying pharmacokinetics of the drugs via preparation of various nanoplatforms. Doxil, a well-known FDA-approved nanoplatform of doxorubicin as antineoplastic agent, is frequently used in clinics in order to reduce cardiotoxicity of doxorubicin. Since Doxil shows some shortcomings in clinics including hand and food syndrome and very slow release pattern thus, there is a demand for the development and preparation of new doxorubicin nanoformulation with fewer side effects. The new formulation of the doxorubicin, synthesized previously by our group was extensively examined in the current study. This new formulation is doxorubicin encapsulated in PEG-PLGA polymersomes (PolyDOX). The main aim of the study was to compare the distribution and treatment efficacy of a new doxorubicin-polymersomal formulation (PolyDOX) with regular liposomal formulation (Doxil-mimic) in murine colon adenocarcinoma model. Additionally, the pathological, hematological changes, pharmacodynamics, biodistribution, tolerated dose and survival rate in vivo were evaluated and compared. Murine colon cancer model was induced by subcutaneous inoculation of BALB/c mice with C26 cells. Afterwards, either Doxil-mimic or PolyDOX was administered intravenously. The obtained results from biodistribution study showed a remarkable difference in the distribution of drugs in murine organs. In this regard, Doxil-mimic exhibited prolonged (48h) presence within liver tissues while PolyDOX preferentially accumulate in tumor and the presence in liver 48h post-treatment was significantly lower than that of Doxil-mimic. Obtained results demonstrated comparable final length of life for mice receiving either Doxil-mimic or PolyDOX formulations whereas tolerated dose of mice receiving Doxil-mimic was remarkably higher than those receiving PolyDOX. Therapeutic efficacy of formulation in term of tumor growth rate

  15. Biomarkers of oxidative stress and cataract. Novel drug delivery therapeutic strategies targeting telomere reduction and the expression of telomerase activity in the lens epithelial cells with N-acetylcarnosine lubricant eye drops: anti-cataract which helps to prevent and treat cataracts in the eyes of dogs and other animals.

    Science.gov (United States)

    Babizhayev, Mark A; Yegorov, Yegor E

    2014-01-01

    Cataracts in small animals are shown to be at least partially caused by oxidative damage to lens epithelial cells (LECs) and the internal lens; biomarkers of oxidative stress in the lens are considered as general biomarkers for life expectancy in the canine and other animals. Telomeres lengths and expressed telomerase activity in canine LECs may serve as important monitors of oxidative damage in normal LECs with documented higher levels of telomerase activity in cataractous LECs during cells' lifespan. Loss of functional telomere length below a critical threshold in LECs of canines during the effect of UV and chronic oxidative stress or metabolic failure, can activate programs leading to LEC senescence or death. Telomerase is induced in LECs of canines at critical stages of cataractogenesis initiation and exposure to oxidative stress through the involvement of catalytically active prooxidant transition metal (iron) ions. This work documents that transition metal ions (such as, ferrous ions- catalytic oxidants) might induce premature senescence in LECs of canines, telomere shortening with increased telomerase activity as adaptive response to UV light, oxidative and metabolic stresses. The therapeutic treatment with 1% N-acetylcarnosine (NAC) prodrug delivery is beneficial for prevention and dissolution of ripe cataracts in canines. This biological activity is based on the findings of ferroxidase activity pertinent to the dipeptide carnosine released ophthalmically from NAC prodrug of L-carnosine, stabilizing properties of carnosine on biological membranes based on the ability of the imidazole-containing dipeptides to interact with lipid peroxidation products and reactive oxygen species (ROS), to prevent membrane damage and delute the associated with membrane fragements protein aggregates. The advent of therapeutic treatment of cataracts in canines with N-acetylcarnosine lubricant eye drops through targeting the prevention of loss of functional telomere length below

  16. Need for appropriate formulations for children: the national institute of child health and human development-pediatric formulations initiative, part 1.

    Science.gov (United States)

    Giacoia, George P; Taylor-Zapata, Perdita; Mattison, Donald

    2007-01-01

    The development and compounding of pharmacotherapeutic formulations that are suitable for infants and young children can be a challenging problem. This problem results from the lack of knowledge on the acceptability of different dosage forms and formulations in children in relation to age and developmental status, as well as the lack of reliable documentation of formulations used in pediatric clinical trials. As part of its mandate under the Best Pharmaceuticals for Children Act to improve pediatric therapeutics, the National Institute of Child Health and Human Development has sponsored the Pediatric Formulation Initiative. The goal of this ongoing initiative is to address the issues and concnerns associated with pediatric therapeutics by convening groups of researchers and experts in pediatric formulations from academia, pharmaceutical companies, the National Institutes of Health, and the U.S. Food and Drug Administration.

  17. Baseline LAW Glass Formulation Testing

    International Nuclear Information System (INIS)

    Kruger, Albert A.; Mooers, Cavin; Bazemore, Gina; Pegg, Ian L.; Hight, Kenneth; Lai, Shan Tao; Buechele, Andrew; Rielley, Elizabeth; Gan, Hao; Muller, Isabelle S.; Cecil, Richard

    2013-01-01

    The major objective of the baseline glass formulation work was to develop and select glass formulations that are compliant with contractual and processing requirements for each of the LAW waste streams. Other objectives of the work included preparation and characterization of glasses with respect to the properties of interest, optimization of sulfate loading in the glasses, evaluation of ability to achieve waste loading limits, testing to demonstrate compatibility of glass melts with melter materials of construction, development of glass formulations to support ILAW qualification activities, and identification of glass formulation issues with respect to contract specifications and processing requirements

  18. Evaluating Suspension Formulations of Theophylline Cocrystals With Artificial Sweeteners.

    Science.gov (United States)

    Aitipamula, Srinivasulu; Wong, Annie B H; Kanaujia, Parijat

    2018-02-01

    Pharmaceutical cocrystals have garnered significant interest as potential solids to address issues associated with formulation development of drug substances. However, studies concerning the understanding of formulation behavior of cocrystals are still at the nascent stage. We present results of our attempts to evaluate suspension formulations of cocrystals of an antiasthmatic drug, theophylline, with 2 artificial sweeteners. Stability, solubility, drug release, and taste of the suspension formulations were evaluated. Suspension that contained cocrystal with acesulfame showed higher drug release rate, while a cocrystal with saccharin showed a significant reduction in drug release rate. The cocrystal with saccharin was found stable in suspension for over 9 weeks at accelerated test condition; in contrast, the cocrystal with acesulfame was found unstable. Taste analysis using an electronic taste-sensing system revealed improved sweetness of the suspension formulations with cocrystals. Theophylline has a narrow therapeutic index with a short half-life which necessitates frequent dosing. This adversely impacts patient compliance and enhances risk of gastrointestinal and cardiovascular adverse effects. The greater thermodynamic stability, sweetness, and sustained drug release of the suspension formulation of theophylline-saccharin could offer an alternative solution to the short half-life of theophylline and make it a promising formulation for treating asthmatic pediatric and geriatric patients. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  19. Use of a new borate raw material for glaze formulation

    International Nuclear Information System (INIS)

    Gomez-Tena, M. P.; Moreno, A.; Bou, E.; Cook, S.; Galindo, M.

    2010-01-01

    The Rio Tinto Minerals company has developed a new borate (E-4972), which can be used in glaze formulation (patent WO 2007/148101). This new borate, synthesised by low-temperature calcination, fundamentally contributes five oxides: silicon oxide (SiO 2 ), aluminium oxide (Al 2 O 3 ), boron oxide (B 2 O 3 ), calcium oxide (CaO), and sodium oxide (Na 2 O), its content in B 2 O 3 being between 10 and 11% by weight. It is largely amorphous, and quartz is the major crystalline phase present. The characteristics of this new borate, such as its low solubility and ability readily to form glassy phase, enable it to be used as a raw material in glaze compositions. Its suitability for glaze formulation has been the result of several years research in collaboration with the Instituto de Tecnologia Ceramica. In this paper, the feasibility has been studied of fabricating ceramic glazes by using a new synthetic borate raw material that contributes boron to the glaze composition without this needing to be done in fritted form. It has been possible to obtain fired glazes with similar technical and aesthetics characteristics to those obtained from industrial glaze compositions that contain typical frits in their compositions, thus enabling glazes to be formulated by using the new synthetic boron raw material. The results obtained show that this new raw material (E-4972) is particularly appropriate for use in producing glazes with low gloss at high temperature. (Author) 15 refs.

  20. Antioxidant effects of an ozonized theobroma oil formulation on damaged-inflammatory rat skin

    Energy Technology Data Exchange (ETDEWEB)

    Sanchez, Y.; Diaz, M.F.; Hernandez, F.; Gila, D.; Ga, G.

    2011-07-01

    The aim of this study was to determine whether a cosmetic formulation elaborated with ozonized theobroma oil may exert beneficial effects in the restoring of the antioxidant activity on the skin of rats previously irradiated with ultraviolet light. 0.5 g of the formulation was applied on the skin of rats for five days. Superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) activity were determined in a homogenate of rat skin. Malondialdehyde (MDA), conjugated dienes (CD) and total hydroperoxide (THP) content were determined as biomarkers of oxidative stress. Using these parameters, antioxidant and oxidant activity, redox index and oxidative stress grade were determined. The total antioxidant activity was significantly increased while the redox index, total oxidant activity and oxidative stress grade decreased significantly in damaged rats treated with the formulation. These results show the antioxidant properties of the cosmetic formulation due to the stimulation of antioxidant enzymes such as SOD and GPx, preventing skin injury induced by ultraviolet irradiation. (Author).

  1. Formulation of Extended-Release Metformin Hydrochloride Matrix ...

    African Journals Online (AJOL)

    Methods: Various metformin hydrochloride formulations containing a hydrophobic carrier (stearic acid) and a hydrophilic polymer (polyethylene oxide) were prepared using a 32 factorial design. ... The release data were subjected to various release kinetic models and also compared with those of a commercial brand.

  2. Cleaning UF membranes with simple and formulated solutions

    NARCIS (Netherlands)

    Levitsky, I.; Duek, A.; Naim, R.; Arkhangelsky, E.; Gitis, V.

    2012-01-01

    The ultrafiltration membranes fouled by proteins are typically cleaned by consecutive soaking in alkali, surfactant and oxidizing solutions. We combined all three chemicals into a formulated cleaning agent and examined its efficiency to restore the water flux without damaging the membrane or

  3. Preparation of nanoscale pulmonary drug delivery formulations by spray drying

    DEFF Research Database (Denmark)

    Bohr, Adam; Ruge, Christian A; Beck-Broichsitter, Moritz

    2014-01-01

    and can offer controlled drug release. There are numerous methods for producing therapeutic nanoparticles, each with their own advantages and suitable application. Liquid atomization techniques such as spray drying can produce nanoparticle formulations in a dry powder form suitable for pulmonary...... administration in a direct one-step process. This chapter describes the different state-of-the-art techniques used to prepare drug nanoparticles (with special emphasize on spray drying techniques) and the strategies for administering such unique formulations to the pulmonary environment....

  4. Reactive Oxygen Species and the Aging Eye: Specific Role of Metabolically Active Mitochondria in Maintaining Lens Function and in the Initiation of the Oxidation-Induced Maturity Onset Cataract--A Novel Platform of Mitochondria-Targeted Antioxidants With Broad Therapeutic Potential for Redox Regulation and Detoxification of Oxidants in Eye Diseases.

    Science.gov (United States)

    Babizhayev, Mark A; Yegorov, Yegor E

    2016-01-01

    The aging eye appears to be at considerable risk from oxidative stress. A great deal of research indicates that dysfunctional mitochondria are the primary site of reactive oxygen species (ROS). More than 95% of O2 produced during normal metabolism is generated by the electron transport chain in the inner mitochondrial membrane. Mitochondria are also the major target of ROS. Cataract formation, the opacification of the eye lens, is one of the leading causes of human blindness worldwide, accounting for 47.8% of all causes of blindness. Cataracts result from the deposition of aggregated proteins in the eye lens and lens fiber cell plasma membrane damage, which causes clouding of the lens, light scattering, and obstruction of vision. ROS-induced damage in the lens cell may consist of oxidation of proteins, DNA damage, and/or lipid peroxidation, all of which have been implicated in cataractogenesis. This article is an attempt to integrate how mitochondrial ROS are altered in the aging eye along with those protective and repair therapeutic systems believed to regulate ROS levels in ocular tissues and how damage to these systems contributes to age-onset eye disease and cataract formation. Mitochondria-targeted antioxidants might be used to effectively prevent ROS-induced oxidation of lipids and proteins in the inner mitochondrial membrane in vivo. As a result of the combination of weak metal chelating, OH and lipid peroxyl radicals scavenging, reducing activities to liberated fatty acid, and phospholipid hydroperoxides, carnosine and carcinine appear to be physiological antioxidants able to efficiently protect the lipid phase of biologic membranes and aqueous environments and act as the antiapoptotic natural drug compounds The authors developed and patented the new ophthalmic compositions, including N-acetylcarnosine, acting as a prodrug of naturally targeted to mitochondria L-carnosine endowed with pluripotent antioxidant activities combined with mitochondria

  5. Long-term delivery of protein therapeutics.

    Science.gov (United States)

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

    2015-03-01

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

  6. Polymorphous light eruption (PLE) and a new potent antioxidant and UVA-protective formulation as prophylaxis.

    Science.gov (United States)

    Hadshiew, I M; Treder-Conrad, C; v Bülow, R; Klette, E; Mann, T; Stäb, F; Moll, I; Rippke, F

    2004-08-01

    Polymorphous light eruption (PLE) is the most common photodermatosis. While its etiology still remains elusive, pathogenesis seems to involve UVA-induced oxidative stress and subsequent deregulation of antioxidative immune responses. Only few and often ineffective prophylactic and therapeutic measures exist to date. In our randomized, double-blind, placebo-controlled clinical study, we compared the efficacy of a new topical formulation, consisting of 0.25%alpha-glucosylrutin (AGR) (a natural, modified flavonoid), 1% tocopheryl acetate (vitamin E) and a broad-spectrum, highly UVA-protective sunscreen (SPF 15) in a hydrodispersion gel vehicle, to a sunscreen-only gel and vehicle. Thirty patients with a history of PLE were pretreated with either the above formulation, a similar preparation (with the same concentration for vitamin E and AGR, but a different UV filter system), placebo or a SPF 15 sunscreen-only gel, 30 min prior to daily photoprovocation with UVA irradiations of 60-100 J/cm(2) to 5 x 5 cm(2) areas on the upper arms. After 4 days, results revealed a statistically highly significant difference (PPLE. While only one patient developed clinical signs of PLE with accompanying itch in the area treated with the new antioxidant UV-protective gel formulation, 62.1% of the placebo-treated areas and 41.3% of the sunscreen-only treated areas showed mild to moderate signs of PLE. Combining a potent antioxidant with a broad-spectrum, highly UVA-protective sunscreen is far more effective in preventing PLE than sunscreen alone or placebo and should thus be employed as the prophylaxis of choice for PLE.

  7. Formulation and Characterization of Aceclofenac -Aloe vera Transemulgel.

    Science.gov (United States)

    Raju, Y Prasanna; Haritha, K; Satyanarayana, Rao P; Vandana, K R; Bindu, D Thushara; Vinesha, V; Chowdary, V Harini

    2015-01-01

    The present research was aimed to formulate aceclofenac transemulgel using Aloe vera as gel base. The prepared formulations were subjected to physical characterization, in-vitro and in-vivo assessment. Aceclofenac, a hydrophobic potential non steroidal anti inflammatory drug, causes ulceration upon chronic oral administration, could be formulated into transemulgel to enhance therapeutic efficacy and to lower the unwanted side effects. The transemulgel was prepared from aqueous Aloe vera gel and aceclofenac emulsion. The prepared transemulgel was evaluated for its pH, viscosity, drug content, skin irritation, in-vitro diffusion and accelerated stability studies. The prepared aceclofenac-Aloe vera tranemulgel and commercial aceclofenac gel were subjected to pharmacodynamic studies in albino rats of Wistar strain employing carrageenan induced left hind paw edema method to assess the anti-inflammatory effect. The transemulgel showed a pH of 6.78 and viscosity of 18 cps. In-vitro diffusion data revealed better permeation characteristics. Topical application of formulation found no skin irritation. Stability study has proved the integrity of the formulation. The prepared aceclofenac Aloe vera transemulgel showed better in-vitro drug release when compared with the commercial aceclofenac gel formulation. Anti-inflammatory activity in treated rats showed the significant paw volume reduction at pAloe vera as gel base.

  8. 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

  9. Neonates need tailored drug formulations.

    Science.gov (United States)

    Allegaert, Karel

    2013-02-08

    Drugs are very strong tools used to improve outcome in neonates. Despite this fact and in contrast to tailored perfusion equipment, incubators or ventilators for neonates, we still commonly use drug formulations initially developed for adults. We would like to make the point that drug formulations given to neonates need to be tailored for this age group. Besides the obvious need to search for active compounds that take the pathophysiology of the newborn into account, this includes the dosage and formulation. The dosage or concentration should facilitate the administration of low amounts and be flexible since clearance is lower in neonates with additional extensive between-individual variability. Formulations need to be tailored for dosage variability in the low ranges and also to the clinical characteristics of neonates. A specific focus of interest during neonatal drug development therefore is a need to quantify and limit excipient exposure based on the available knowledge of their safety or toxicity. Until such tailored vials and formulations become available, compounding practices for drug formulations in neonates should be evaluated to guarantee the correct dosing, product stability and safety.

  10. Microcanonical formulation of quantum field theories

    International Nuclear Information System (INIS)

    Iwazaki, A.

    1984-03-01

    A microcanonical formulation of Euclidean quantum field theories is presented. In the formulation, correlation functions are given by a microcanonical ensemble average of fields. Furthermore, the perturbative equivalence of the formulation and the standard functional formulation is proved and the equipartition low is derived in our formulation. (author)

  11. Design of amphotericin B oral formulation for antifungal therapy.

    Science.gov (United States)

    Liu, Min; Chen, Meiwan; Yang, Zhiwen

    2017-11-01

    Amphotericin B (AmB) remains the "gold standard" for systemic antifungal therapy, even though new drugs are emerging as the attractive antifungal agents. Since AmB has negligible oral absorption as a consequence of its unfavorable physicochemical characterizations, its use is restricted to parenteral administration which is accompanied by severe side effects. As greater understanding of the gastrointestinal tract has developed, the advanced drug delivery systems are emerging with the potential to overcome the barriers of AmB oral delivery. Much research has demonstrated that oral AmB formulations such as lipid formulations may have beneficial therapeutic efficacy with reduced adverse effects and suitable for clinical application. Here we reviewed the different formulation strategies to enhance oral drug efficacy, and discussed the current trends and future perspectives for AmB oral administration in the treatment of antifungal infections.

  12. Combinatorial therapy of exercise-preconditioning and nanocurcumin formulation supplementation improves cardiac adaptation under hypobaric hypoxia.

    Science.gov (United States)

    Nehra, Sarita; Bhardwaj, Varun; Bansal, Anju; Saraswat, Deepika

    2017-09-26

    Chronic hypobaric hypoxia (cHH) mediated cardiac insufficiencies are associated with pathological damage. Sustained redox stress and work load are major causative agents of cardiac insufficiencies under cHH. Despite the advancements made in pharmacological (anti-oxidants, vasodilators) and non-pharmacological therapeutics (acclimatization strategies and schedules), only partial success has been achieved in improving cardiac acclimatization to cHH. This necessitates the need for potent combinatorial therapies to improve cardiac acclimatization at high altitudes. We hypothesize that a combinatorial therapy comprising preconditioning to mild aerobic treadmill exercise and supplementation with nanocurcumin formulation (NCF) consisting of nanocurcumin (NC) and pyrroloquinoline quinone (PQQ) might improve cardiac adaptation at high altitudes. Adult Sprague-Dawley rats pre-conditioned to treadmill exercise and supplemented with NCF were exposed to cHH (7620 m altitude corresponding to pO2~8% at 28±2°C, relative humidity 55%±1%) for 3 weeks. The rat hearts were analyzed for changes in markers of oxidative stress (free radical leakage, lipid peroxidation, manganese-superoxide dismutase [MnSOD] activity), cardiac injury (circulating cardiac troponin I [TnI] and T [cTnT], myocardial creatine kinase [CK-MB]), metabolic damage (lactate dehydrogenase [LDH] and acetyl-coenzyme A levels, lactate and pyruvate levels) and bio-energetic insufficiency (ATP, p-AMPKα). Significant modulations (p≤0.05) in cardiac redox status, metabolic damage, cardiac injury and bio-energetics were observed in rats receiving both NCF supplementation and treadmill exercise-preconditioning compared with rats receiving only one of the treatments. The combinatorial therapeutic strategy showed a tremendous improvement in cardiac acclimatization to cHH compared to either exercise-preconditioning or NCF supplementation alone which was evident from the effective modulation in redox, metabolic, contractile

  13. Tactile friction of topical formulations.

    Science.gov (United States)

    Skedung, L; Buraczewska-Norin, I; Dawood, N; Rutland, M W; Ringstad, L

    2016-02-01

    The tactile perception is essential for all types of topical formulations (cosmetic, pharmaceutical, medical device) and the possibility to predict the sensorial response by using instrumental methods instead of sensory testing would save time and cost at an early stage product development. Here, we report on an instrumental evaluation method using tactile friction measurements to estimate perceptual attributes of topical formulations. Friction was measured between an index finger and an artificial skin substrate after application of formulations using a force sensor. Both model formulations of liquid crystalline phase structures with significantly different tactile properties, as well as commercial pharmaceutical moisturizing creams being more tactile-similar, were investigated. Friction coefficients were calculated as the ratio of the friction force to the applied load. The structures of the model formulations and phase transitions as a result of water evaporation were identified using optical microscopy. The friction device could distinguish friction coefficients between the phase structures, as well as the commercial creams after spreading and absorption into the substrate. In addition, phase transitions resulting in alterations in the feel of the formulations could be detected. A correlation was established between skin hydration and friction coefficient, where hydrated skin gave rise to higher friction. Also a link between skin smoothening and finger friction was established for the commercial moisturizing creams, although further investigations are needed to analyse this and correlations with other sensorial attributes in more detail. The present investigation shows that tactile friction measurements have potential as an alternative or complement in the evaluation of perception of topical formulations. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Dissolution studies on Nickel ferrite in dilute chemical decontamination formulations

    Energy Technology Data Exchange (ETDEWEB)

    Ranganathan, S. [New Brunswick Univ., Fredericton, NB (Canada). Dept. of Chemical Engineering; Srinivasan, M.P. [Bhabha Atomic Research Centre (BARC) (India). Water and Steam Chemistry Laboratory; Raghavan, P.S. [Madras Christian College, Chennai (India); Narasimhan, S.V. [Bhabha Atomic Research Centre, Bombay (India); Gopalan, R. [Madras Christian College, Chennai (India). Department of Chemistry

    2004-09-01

    Nickel ferrite is one of the important corrosion products in the pipeline surfaces of water-cooled nuclear reactors. The dissolution of the nickel ferrite by chelating agents is very sensitive to the nature of the chelant, the nature of the reductant used in the formulation and the temperature at which the dissolution studies are performed. The dissolution is mainly controlled by the reductive dissolution of the ferrite particles, but complexing agents also play a significant role in the dissolution process. This study deals with the leaching of iron and nickel from nickel ferrite prepared by the solid-state method. The dissolution studies are performed in pyridine-2,6-dicarboxylic acid (PDCA), nitrilotriacetic acid (NTA), and ethylenediaminetetraacetic acid (EDTA) formulations containing organic reductants like ascorbic acid and low oxidation state transition metal ion reductants like Fe(II)-L (where L = PDCA, NTA, EDTA) at 85 C. The dissolution of nickel ferrite in PDCA, NTA and EDTA formulations is influenced by the presence of reductants in the formulations. The addition of Fe(II)-L in the formulation greatly enhances the dissolution of nickel ferrite. The preferential leaching of nickel over iron during the dissolution of nickel ferrite was observed in all the formulations. (orig.)

  15. Dissolution studies on Nickel ferrite in dilute chemical decontamination formulations

    International Nuclear Information System (INIS)

    Ranganathan, S.; Narasimhan, S.V.; Gopalan, R.

    2004-01-01

    Nickel ferrite is one of the important corrosion products in the pipeline surfaces of water-cooled nuclear reactors. The dissolution of the nickel ferrite by chelating agents is very sensitive to the nature of the chelant, the nature of the reductant used in the formulation and the temperature at which the dissolution studies are performed. The dissolution is mainly controlled by the reductive dissolution of the ferrite particles, but complexing agents also play a significant role in the dissolution process. This study deals with the leaching of iron and nickel from nickel ferrite prepared by the solid-state method. The dissolution studies are performed in pyridine-2,6-dicarboxylic acid (PDCA), nitrilotriacetic acid (NTA), and ethylenediaminetetraacetic acid (EDTA) formulations containing organic reductants like ascorbic acid and low oxidation state transition metal ion reductants like Fe(II)-L (where L = PDCA, NTA, EDTA) at 85 C. The dissolution of nickel ferrite in PDCA, NTA and EDTA formulations is influenced by the presence of reductants in the formulations. The addition of Fe(II)-L in the formulation greatly enhances the dissolution of nickel ferrite. The preferential leaching of nickel over iron during the dissolution of nickel ferrite was observed in all the formulations. (orig.)

  16. Liposomal Formulations in Clinical Use: An Updated Review

    Directory of Open Access Journals (Sweden)

    Upendra Bulbake

    2017-03-01

    Full Text Available Liposomes are the first nano drug delivery systems that have been successfully translated into real-time clinical applications. These closed bilayer phospholipid vesicles have witnessed many technical advances in recent years since their first development in 1965. Delivery of therapeutics by liposomes alters their biodistribution profile, which further enhances the therapeutic index of various drugs. Extensive research is being carried out using these nano drug delivery systems in diverse areas including the delivery of anti-cancer, anti-fungal, anti-inflammatory drugs and therapeutic genes. The significant contribution of liposomes as drug delivery systems in the healthcare sector is known by many clinical products, e.g., Doxil®, Ambisome®, DepoDur™, etc. This review provides a detailed update on liposomal technologies e.g., DepoFoam™ Technology, Stealth technology, etc., the formulation aspects of clinically used products and ongoing clinical trials on liposomes.

  17. Decontamination formulation with sorbent additive

    Science.gov (United States)

    Tucker; Mark D. , Comstock; Robert H.

    2007-10-16

    A decontamination formulation and method of making that neutralizes the adverse health effects of both chemical and biological compounds, especially chemical warfare (CW) and biological warfare (BW) agents, and toxic industrial chemicals. The formulation provides solubilizing compounds that serve to effectively render the chemical and biological compounds, particularly CW and BW compounds, susceptible to attack, and at least one reactive compound that serves to attack (and detoxify or kill) the compound. The formulation includes at least one solubilizing agent, a reactive compound, a bleaching activator, a sorbent additive, and water. The highly adsorbent, water-soluble sorbent additive (e.g., sorbitol or mannitol) is used to "dry out" one or more liquid ingredients, such as the liquid bleaching activator (e.g., propylene glycol diacetate or glycerol diacetate) and convert the activator into a dry, free-flowing powder that has an extended shelf life, and is more convenient to handle and mix in the field.

  18. Influence of Differing Analgesic Formulations of Aspirin on Pharmacokinetic Parameters

    Directory of Open Access Journals (Sweden)

    Kunal Kanani

    2015-08-01

    Full Text Available Aspirin has been used therapeutically for over 100 years. As the originator and an important marketer of aspirin-containing products, Bayer’s clinical trial database contains numerous reports of the pharmacokinetics of various aspirin formulations. These include evaluations of plain tablets, effervescent tablets, granules, chewable tablets, and fast-release tablets. This publication seeks to expand upon the available pharmacokinetic information concerning aspirin formulations. In the pre-systemic circulation, acetylsalicylic acid (ASA is rapidly converted into its main active metabolite, salicylic acid (SA. Therefore, both substances are measured in plasma and reported in the results. The 500 mg strength of each formulation was chosen for analysis as this is the most commonly used for analgesia. A total of 22 studies were included in the analysis. All formulations of 500 mg aspirin result in comparable plasma exposure to ASA and SA as evidenced by AUC. Tablets and dry granules provide a consistently lower Cmax compared to effervescent, granules in suspension and fast release tablets. Effervescent tablets, fast release tablets, and granules in suspension provide a consistently lower median Tmax compared to dry granules and tablets for both ASA and SA. This report reinforces the importance of formulation differences and their impact on pharmacokinetic parameters.

  19. Sugar-based amphiphilic polymers for biomedical applications: from nanocarriers to therapeutics.

    Science.gov (United States)

    Gu, Li; Faig, Allison; Abdelhamid, Dalia; Uhrich, Kathryn

    2014-10-21

    disease. The atherosclerotic cascade is usually triggered by the unregulated uptake of oxidized low-density lipoprotein, a cholesterol carrier, in macrophages of the blood vessel wall; SBAPs can significantly inhibit oxidized low-density lipoprotein uptake in macrophages and abrogate the atherosclerotic cascade. By modification of various functionalities (e.g., branching, stereochemistry, hydrophobicity, and charge) in the SBAP chemical structure, SBAP bioactivity was optimized, and influential structural components were identified. Despite the potential of SBAPs as atherosclerotic therapies, blood stability of the SBAP micelles was not ideal for in vivo applications, and means to stabilize them were pursued. Using kinetic entrapment via flash nanoprecipitation, SBAPs were formulated into nanoparticles with a hydrophobic solute core and SBAP shell. SBAP nanoparticles exhibited excellent physiological stability and enhanced bioactivity compared with SBAP micelles. Further, this method enables encapsulation of additional hydrophobic drugs (e.g., vitamin E) to yield a stable formulation that releases two bioactives. Both as nanoscale carriers and as polymer therapeutics, SBAPs are promising biomaterials for medical applications.

  20. Review of the pharmaceutical properties and clinical effects of the topical NSAID formulation, diclofenac epolamine.

    Science.gov (United States)

    Rainsford, K D; Kean, W F; Ehrlich, G E

    2008-10-01

    Topical formulations of non-steroidal anti-inflammatory drugs (NSAIDs), in particular diclofenac (DI), have become popular for treating various acute and chronic painful inflammatory conditions. To perform a literature review of (1) the use of topical NSAIDs; (2) the pharmaceutical, pharmacokinetic and pharmacodynamic properties of a medicated plaster (patch) containing diclofenac epolamine (DI-EP, Flector Tissugel, Flector patch) compared with other formulations of topical NSAIDs; and (3) evaluation of the clinical findings from studies with this novel DI-EP patch. (1) Pharmacokinetic studies involved determination of DI from DI-EP and separately epolamine (EP) and the epoxide metabolite (N-oxide-EP) in laboratory animals and humans; the latter being the major metabolite in humans. About 2% of DI is absorbed by the skin in humans and is excreted in the urine. Maximum plasma concentrations of 17.4 ng/mL DI are reached at 5.4 hours (approximate steady state conditions); the plasma elimination half-time (t(1/2)) being 26.4 hours. Low systemic levels of DI and EP are produced from DI-EP. Pronounced accumulation of DI occurs in the muscle layers and in synovial fluids of arthritic patients; (2) No significant toxicity occurs from EP nor N-oxide-EP, while that of oral DI-EP was similar to that from DI; and (3) In acute musculoskeletal conditions (sprains, tendonitis and sports injuries) and osteoarthritis DI-EP patches control pain and signs of joint or physical injury compared with placebo controls by 3-5 days with almost complete pain relief at 14 days. DI-EP was shown to have equivalent therapeutic effect to another DI diethylammonium gel formulation (Voltaren Emulgel). There were no reports of serious adverse events in the gastro-intestinal (GI) tract, kidneys or liver from DI-EP. Mild GI symptoms and skin reactions occur in 2 and 10% of patients, respectively. The patch delivery of DI in DI-EP affords controlled delivery of the active drug in contrast to that from

  1. Curcumin nanodisks: formulation and characterization

    OpenAIRE

    Ghosh, Mistuni; Singh, Amareshwar T. K.; Xu, Wenwei; Sulchek, Todd; Gordon, Leo I.; Ryan, Robert O.

    2010-01-01

    Nanodisks (ND) are nanoscale, disk-shaped phospholipid bilayers whose edge is stabilized by apolipoproteins. In the present study, ND were formulated with the bioactive polyphenol, curcumin, at a 6:1 phospholipid:curcumin molar ratio. Atomic force microscopy revealed that curcumin-ND are particles with diameters

  2. Covariant Formulation of Hooke's Law.

    Science.gov (United States)

    Gron, O.

    1981-01-01

    Introducing a four-vector strain and a four-force stress, Hooke's law is written as a four-vector equation. This formulation is shown to clarify seemingly paradoxical results in connection with uniformly accelerated motion, and rotational motion with angular acceleration. (Author/JN)

  3. Hamiltonian formulation of the supermembrane

    International Nuclear Information System (INIS)

    Bergshoeff, E.; Sezgin, E.; Tanii, Y.

    1987-06-01

    The Hamiltonian formulation of the supermembrane theory in eleven dimensions is given. The covariant split of the first and second class constraints is exhibited, and their Dirac brackets are computed. Gauge conditions are imposed in such a way that the reparametrizations of the membrane with divergence free 2-vectors are unfixed. (author). 10 refs

  4. Curcumin as a potential therapeutic candidate for Helicobacter pylori associated diseases

    Science.gov (United States)

    Sarkar, Avijit; De, Ronita; Mukhopadhyay, Asish K

    2016-01-01

    Curcumin, a yellow pigment and principal polyphenolic Curcuminoid obtained from the turmeric rhizome Curcuma longa, is commonly used as a food-coloring agent. Studies suggest that curcumin has a wide range of beneficial properties e.g., anti-inflammatory, anti-oxidant, anti-cancer, anti-proliferative, anti-fungal and anti-microbial. These pleiotropic activities prompted several research groups to elucidate the role of curcumin in Helicobacter pylori (H. pylori) infection. This is the first review with this heading where we discussed regarding the role of curcumin as an anti-H. pylori agent along with its potential in other gastrointestinal diseases. Based on several in vitro, early cell culture, animal research and few pre-clinical trials, curcumin projected as a potential therapeutic candidate against H. pylori mediated gastric pathogenesis. This review sheds light on the anti-H. pylori effects of curcumin in different models with meticulous emphasis on its anti-oxidant, anti-inflammatory and anti-carcinogenic effects as well as some critical signaling and effecter molecules. Remarkably, non-toxic molecule curcumin fulfills the characteristics for an ideal chemopreventive agent against H. pylori mediated gastric carcinogenesis but the foremost challenge is to obtain the optimum therapeutic levels of curcumin, due to its low solubility and poor bioavailability. Further, we have discussed about the possibilities for improving its efficacy and bioavailability. Lastly, we concluded with the anticipation that in near future curcumin may be used to develop a therapeutic drug against H. pylori mediated gastric ailments through improved formulation or delivery systems, facilitating its enhanced absorption and cellular uptake. PMID:26973412

  5. Implication of Formulation Strategies on the Bioavailability of Selected Plant-Derived Hepatoprotectants.

    Science.gov (United States)

    Dash, Ranjeet Prasad; Kala, Manika; Nivsarkar, Manish; Babu, R Jayachandra

    2017-01-01

    Plant-derived active ingredients with hepatoprotective activity have been used extensively in the treatment of various liver diseases. These compounds are used either in their natural form or the chemical constituents present therein serve as templates for the development of synthetic-based therapeutic entities. Current research interests are focused on formulation development and pharmacokinetic studies of herbal medicines. This article provides a comprehensive review on formulation influences on the preclinical/clinical pharmacokinetics of selected hepatoprotectants such as silymarin, curcumin, glycyrrhizin, andrographolide, phyllanthin, hypophyllanthin, and picroside I and II. Both the formulation and pharmacokinetic factors could affect the target-site concentrations of the active herbal components and, thus, the therapeutic responses. This review contributes to the establishment of a comprehensive understanding of the influence of formulation/dosage form on the pharmacokinetic profile of the hepatoprotective compounds.

  6. Protein engineering of subtilisins to improve stability in detergent formulations.

    Science.gov (United States)

    von der Osten, C; Branner, S; Hastrup, S; Hedegaard, L; Rasmussen, M D; Bisgård-Frantzen, H; Carlsen, S; Mikkelsen, J M

    1993-03-01

    Microbial proteases are used extensively in a large number of industrial processes and most importantly in detergent formulations facilitating the removal of proteinaceous stains. Site-directed mutagenesis has been employed in the construction of subtilisin variants with improved storage and oxidation stabilities. It is shown that in spite of significant structural homology between subtilisins subjected to protein engineering the effects of specific mutations can be quite different. Mutations that stabilize one subtilisin may destabilize another.

  7. Walnut supplementation reverses the scopolamine-induced memory impairment by restoration of cholinergic function via mitigating oxidative stress in rats: a potential therapeutic intervention for age related neurodegenerative disorders.

    Science.gov (United States)

    Haider, Saida; Batool, Zehra; Ahmad, Saara; Siddiqui, Rafat Ali; Haleem, Darakhshan Jabeen

    2018-02-01

    The brain is highly susceptible to the damaging effects of oxidative reactive species. The free radicals which are produced as a consequence of aerobic respiration can cause cumulative oxygen damage which may lead to age-related neurodegeneration. Scopolamine, the anti-muscarinic agent, induces amnesia and oxidative stress similar to that observed in the older age. Studies suggest that antioxidants derived from plant products may provide protection against oxidative stress. Therefore, the present study was designed to investigate the attenuation of scopolamine-induced memory impairment and oxidative stress by walnut supplementation in rats. Rats in test group were administrated with walnut suspension (400 mg/kg/day) for four weeks. Both control and walnut-treated rats were then divided into saline and scopolamine-treated groups. Rats in the scopolamine group were injected with scopolamine (0.5 mg/kg dissolved in saline) five minutes before the start of each memory test. Memory was assessed by elevated plus maze (EPM), Morris water maze (MWM), and novel object recognition task (NOR) followed by estimation of regional acetylcholine levels and acetylcholinesterase activity. In the next phase, brain oxidative status was determined by assaying lipid peroxidation, and measuring superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) activities. Results showed that scopolamine-treatment impaired memory function, caused cholinergic dysfunction, and induced oxidative stress in rats compared to that saline-treated controls. These impairments were significantly restored by pre-administration of walnut. This study demonstrates that antioxidant properties of walnut may provide augmented effects on cholinergic function by reducing oxidative stress and thus improving memory performance.

  8. Formulation, Development and Evaluation of delayed release capsules of Duloxetine Hydrochloride made of different Enteric Polymers

    OpenAIRE

    Pallavi Yerramsetty; J. Vijaya Ratna; Venkata Ramana Reddy; Praveen Kumar

    2012-01-01

    Delayed release systems have acquired a centre stage in the arena of pharmaceutical research and development. The present study involves formulation and evaluation of Duloxetine Hydrochloride delayed release capsules. Duloxetine Hydrochloride is an acid labile drug. It degrades in the acidic environment of the stomach thus leading to therapeutic inefficacy. Therefore it is necessary to bypass the acidic pH of the stomach which can be achieved by formulating delayed release dosage form by usin...

  9. Development of chemical cleaning formulation for service water system of FBTR

    International Nuclear Information System (INIS)

    Velmurugan, S.; Narasimhan, S.V.; Das, P.C.; Mathur, P.K.

    1995-01-01

    Service water system of Fast Breeder Test Reactor (FBTR) was found to be corroded and at few locations, the corrosion product oxides were choking the smaller diameter pipelines. An attempt was made to develop a chemical cleaning formulation to chemically remove the oxides using a surface conditioner and chelating agents. Of the several complexants tested, hydroxyethylethylene diamine tetraacetic acid (HEDTA) was found to be better than other complexants from the point of view of oxide dissolution efficiency, solubility etc. A two stage chemical cleaning process involving conditioning of the oxide layer with 0.1% tannic acid followed by exposure of the conditioned oxide layer with a formulation containing 1% HEDTA + 0.5% Sodium Gluconate +0.2% hexamine was recommended to remove the corrosion product oxide present in the service water system. (author). 4 refs., 2 tabs

  10. Beneficial effects of a pyrroloquinolinequinone-containing dietary formulation on motor deficiency, cognitive decline and mitochondrial dysfunction in a mouse model of Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Darrell Sawmiller

    2017-04-01

    Full Text Available Alzheimer’s disease (AD, a progressive neurodegenerative disorder, is linked to oxidative stress, altered amyloid precursor protein (APP proteolysis, tau hyperphosphorylation and the accumulation of amyloid-β (Aβ plaques and neurofibrillary tangles (NFT. A growing body of evidence suggests that mitochondrial dysfunction can be a key promoter of all of these pathologies and predicts that restoration of mitochondrial function might be a potential therapeutic strategy for AD. Therefore, in the present study, we tested the beneficial effect of a nutraceutical formulation Nutrastem II (Nutra II, containing NT020 (a mitochondrial restorative and antioxidant proprietary formulation and pyrroloquinolinequinone (PQQ, a stimulator of mitochondria biogenesis in 5XFAD transgenic mice. Animals were fed Nutra II for 12 weeks, starting at 3 months of age, after which behavioral and neuropathological endpoints were determined. The data from behavioral test batteries clearly revealed that dietary supplementation of Nutra II effectively ameliorated the motor deficiency and cognitive impairment of 5XFAD mice. In addition, Nutra II also protected mitochondrial function in 5XFAD mice brain, as evidenced by declined ROS levels and membrane hyperpolarization, together with elevated ATP levels and respiratory states. Interestingly, while Nutra II treatment only slightly reduced soluble Aβ42 levels, this formulation significantly impacted tau metabolism, as shown by reduced total and phosphorylated tau levels of 5XFAD mouse brain. Taken together, these preclinical findings confirm that mitochondrial function may be a key treatment target for AD and that Nutra II should be further investigated as a potential candidate for AD therapy.

  11. Therapeutic Oligonucleotides Targeting Liver Disease: TTR Amyloidosis

    Directory of Open Access Journals (Sweden)

    Christoph Niemietz

    2015-09-01

    Full Text Available The liver has become an increasingly interesting target for oligonucleotide therapy. Mutations of the gene encoding transthyretin (TTR, expressed in vast amounts by the liver, result in a complex degenerative disease, termed familial amyloid polyneuropathy (FAP. Misfolded variants of TTR are linked to the establishment of extracellular protein deposition in various tissues, including the heart and the peripheral nervous system. Recent progress in the chemistry and formulation of antisense (ASO and small interfering RNA (siRNA designed for a knockdown of TTR mRNA in the liver has allowed to address the issue of gene-specific molecular therapy in a clinical setting of FAP. The two therapeutic oligonucleotides bind to RNA in a sequence specific manner but exploit different mechanisms. Here we describe major developments that have led to the advent of therapeutic oligonucleotides for treatment of TTR-related disease.

  12. Langevin formulation of quantum dynamics

    International Nuclear Information System (INIS)

    Roncadelli, M.

    1989-03-01

    We first show that nonrelativistic quantum mechanics formulated at imaginary-(h/2 π) can formally be viewed as the Fokker-Planck description of a frictionless brownian motion, which occurs (in general) in an absorbing medium. We next offer a new formulation of quantum mechanics, which is basically the Langevin treatment of this brownian motion. Explicitly, we derive a noise-average representation for the transition probability W(X'',t''|X',t'), in terms of the solutions to a Langevin equation with a Gaussian white-noise. Upon analytic continuation back to real-(h/2 π),W(X'',t''|X',t') becomes the propagator of the original Schroedinger equation. Our approach allows for a straightforward application to quantum dynamical problems of the mathematical techniques of classical stochastic processes. Moreover, computer simulations of quantum mechanical systems can be carried out by using numerical programs based on the Langevin dynamics. (author). 19 refs, 1 tab

  13. Stability of buffer-free freeze-dried formulations: A feasibility study of a monoclonal antibody at high protein concentrations.

    Science.gov (United States)

    Garidel, Patrick; Pevestorf, Benjamin; Bahrenburg, Sven

    2015-11-01

    We studied the stability of freeze-dried therapeutic protein formulations over a range of initial concentrations (from 40 to 160 mg/mL) and employed a variety of formulation strategies (including buffer-free freeze dried formulations, or BF-FDF). Highly concentrated, buffer-free liquid formulations of therapeutic monoclonal antibodies (mAbs) have been shown to be a viable alternative to conventionally buffered preparations. We considered whether it is feasible to use the buffer-free strategy in freeze-dried formulations, as an answer to some of the known drawbacks of conventional buffers. We therefore conducted an accelerated stability study (24 weeks at 40 °C) to assess the feasibility of stabilizing freeze-dried formulations without "classical" buffer components. Factors monitored included pH stability, protein integrity, and protein aggregation. Because the protein solutions are inherently self-buffering, and the system's buffer capacity scales with protein concentration, we included highly concentrated buffer-free freeze-dried formulations in the study. The tested formulations ranged from "fully formulated" (containing both conventional buffer and disaccharide stabilizers) to "buffer-free" (including formulations with only disaccharide lyoprotectant stabilizers) to "excipient-free" (with neither added buffers nor stabilizers). We evaluated the impacts of varying concentrations, buffering schemes, pHs, and lyoprotectant additives. At the end of 24 weeks, no change in pH was observed in any of the buffer-free formulations. Unbuffered formulations were found to have shorter reconstitution times and lower opalescence than buffered formulations. Protein stability was assessed by visual inspection, sub-visible particle analysis, protein monomer content, charge variants analysis, and hydrophobic interaction chromatography. All of these measures found the stability of buffer-free formulations that included a disaccharide stabilizer comparable to buffer

  14. Applications of inorganic nanoparticles as therapeutic agents

    Science.gov (United States)

    Kim, Taeho; Hyeon, Taeghwan

    2014-01-01

    During the last decade, various functional nanostructured materials with interesting optical, magnetic, mechanical and chemical properties have been extensively applied to biomedical areas including imaging, diagnosis and therapy. In therapeutics, most research has focused on the application of nanoparticles as potential delivery vehicles for drugs and genes, because nanoparticles in the size range of 2-100 nm can interact with biological systems at the molecular level, and allow targeted delivery and passage through biological barriers. Recent investigations have even revealed that several kinds of nanomaterials are intrinsically therapeutic. Not only can they passively interact with cells, but they can also actively mediate molecular processes to regulate cell functions. This can be seen in the treatment of cancer via anti-angiogenic mechanisms as well as the treatment of neurodegenerative diseases by effectively controlling oxidative stress. This review will present recent applications of inorganic nanoparticles as therapeutic agents in the treatment of disease.

  15. Optimization of chlorphenesin emulgel formulation

    OpenAIRE

    Mohamed, Magdy I.

    2004-01-01

    This study was conducted to develop an emulgel formulation of chlorphenesin (CHL) using 2 types of gelling agents: hydroxypropylmethyl cellulose (HPMC) and Carbopol 934. The influence of the type of the gelling agent and the concentration of both the oil phase and emulsifying agent on the drug release from the prepared emulgels was investigated using a 23 factorial design. The prepared emulgels were evaluated for their physical appearance, rheological behavior, drug release, antifungal activi...

  16. Anti-Inflammatory Effects of Novel Standardized Solid Lipid Curcumin Formulations.

    Science.gov (United States)

    Nahar, Pragati P; Slitt, Angela L; Seeram, Navindra P

    2015-07-01

    Inflammation and the presence of pro-inflammatory cytokines are associated with numerous chronic diseases such as type-2 diabetes mellitus, cardiovascular disease, Alzheimer's disease, and cancer. An overwhelming amount of data indicates that curcumin, a polyphenol obtained from the Indian spice turmeric, Curcuma longa, is a potential chemopreventive agent for treating certain cancers and other chronic inflammatory diseases. However, the low bioavailability of curcumin, partly due to its low solubility and stability in the digestive tract, limits its therapeutic applications. Recent studies have demonstrated increased bioavailability and health-promoting effects of a novel solid lipid particle formulation of curcumin (Curcumin SLCP, Longvida(®)). The goal of this study was to evaluate the aqueous solubility and in vitro anti-inflammatory effects of solid lipid curcumin particle (SLCP) formulations using lipopolysaccharide (LPS)-stimulated RAW 264.7 cultured murine macrophages. SLCPs treatment significantly decreased nitric oxide (NO) and prostaglandin-E2 (PGE2) levels at concentrations ranging from 10 to 50 μg/mL, and reduced interleukin-6 (IL-6) levels in a concentration-dependent manner. Transient transfection experiments using a nuclear factor-kappa B (NF-κB) reporter construct indicate that SLCPs significantly inhibit the transcriptional activity of NF-κB in macrophages. Taken together, these results show that in RAW 264.7 murine macrophages, SLCPs have improved solubility over unformulated curcumin, and significantly decrease the LPS-induced pro-inflammatory mediators NO, PGE2, and IL-6 by inhibiting the activation of NF-κB.

  17. Need for appropriate formulations for children: the national institute of child health and human development-pediatric formulations initiative, part 2.

    Science.gov (United States)

    Giacoia, George P; Taylor-Zapata, Perdita; Mattison, Donald

    2007-01-01

    The development and compounding of pharmacotherapeutic formulations that are suitable for infants and young children can be a challenging problem. This problem results from the lack of knowledge on the acceptability of different dosage forms and formulations to children in relation to age and developmental status, as well as the lack of reliable documentation of formulations used in pediatric clinical trials. As part of its mandate under the Best Pharmaceuticals for Children Act to improve pediatric therapeutics, the National Institute of Child Health and Human Development has sponsored the Pediatric Formulations Initiative. The goal of this ongoing initiative is to address the issues and concerns associated with pediatric therapeutics by convening groups of researchers and experts in pediatric formulations from academia, pharmaceutical companies, the National Institutes of Health, and the U.S. Food and Drug Administration. In this second part of a two-part article, the activities of the various groups that constitute the Pediatric Formulations Initiative are discussed, in addition the Initiative's future activities and plans are outlined.

  18. Telomere Attrition in Human Lens Epithelial Cells Associated with Oxidative Stress Provide a New Therapeutic Target for the Treatment, Dissolving and Prevention of Cataract with N-Acetylcarnosine Lubricant Eye Drops. Kinetic, Pharmacological and Activity-Dependent Separation of Therapeutic Targeting: Transcorneal Penetration and Delivery of L-Carnosine in the Aqueous Humor and Hormone-Like Hypothalamic Antiaging Effects of the Instilled Ophthalmic Drug Through a Safe Eye Medication Technique.

    Science.gov (United States)

    Babizhayev, Mark A; Yegorov, Yegor E

    2016-01-01

    the lens response to oxidative damages, aging and health, cataract versus neuroendocrine regulation and disease. The cumulative results demonstrate that carnosine, released ophthalmically from the patented 1% Nacetylcarnosine prodrug lubricant eye drops, at physiological concentration might remarkably reduce the rate of telomere shortening in the lens cells subjected to oxidative stress in the lack of efficient antioxidant lens protection. Carnosine promotes the protection of normal cells from acquiring phenotypic characteristics of cellular senescence. The data of visual functions (visual acuity, glare sensitivity) in older adult subjects and older subjects with cataract treated with 1% N-acetylcarnosine lubricant eye drops showed significant improvement as compared, by contrast with the control group which showed generally no improvement in visual functions, with no difference from baseline in visual acuity and glare sensitivity readings. N-acetylcarnosine derived from the lubricant eye drops may be transported into the hypothalamic tuberomammillary nucleus (TMN) histamine neurons and gradually hydrolyzed. The resulting L-histidine may subsequently be converted into histamine, which could be responsible for the effects of carnosine on neurotransmission and hormone-like antiaging and anti-cataract physiological function. The research utilizing the N-acetylcarnosine lubricant eye drops powerful therapeutic platform provides the findings related to the intraocular uptake exposure sources as well as a timing dosage and duration systemic absorption of said preparation from the conjunctional sac reaching the hypothalamus with activities transfer into the hypothalamic-neuroendocrine pathways affecting across the hypothalamus metabolic pathway the telomere biology and cataract disease occurrence, reversal and prevention and the average expected lifespan of an individual. Such findings can be translated into clinical practice and may provide a basis for personalized cataract

  19. Botulinum neurotoxin formulations: overcoming the confusion

    Directory of Open Access Journals (Sweden)

    Samizadeh S

    2018-05-01

    Full Text Available Souphiyeh Samizadeh,1 Koenraad De Boulle2 1Great British Academy of Aesthetic Medicine, London, UK; 2Aalst Dermatology Clinic, Aalst, Belgium Abstract: Botulinum toxin A is produced by anaerobic spore-forming bacteria and is used for various therapeutic and cosmetic purposes. Botulinum toxin A injections are the most popular nonsurgical procedure worldwide. Despite an increased demand for botulinum toxin A injections, the clinical pharmacology and differences in formulation of commonly available products are poorly understood. The various products available in the market are unique and vary in terms of units, chemical properties, biological activities, and weight, and are therefore not interchangeable. For safe clinical practice and to achieve optimal results, the practitioners need to understand the clinical issues of potency, conversion ratio, and safety issues (toxin spread and immunogenicity. In this paper, the basic clinical pharmacology of botulinum toxin A and differences between onabotulinum toxin A, abobotulinum toxin A, and incobotulinum toxin A are discussed. Keywords: botulinum toxin, botulinum neurotoxin, moiety, protein complexes

  20. Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

    Directory of Open Access Journals (Sweden)

    Danbo Yang

    2010-12-01

    Full Text Available The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(L-g-glutamylglutamine-paclitaxel nano-conjugate (PGG-PTX. PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic.

  1. Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

    International Nuclear Information System (INIS)

    Yang, Danbo; Yu, Lei; Van, Sang

    2010-01-01

    The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(l-γ-glutamylglutamine)-paclitaxel nano-conjugate (PGG-PTX). PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic

  2. Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Danbo [Biomedical Engineering and Technology Institute, Institutes for Advanced Interdisciplinary Research, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062 (China); Yu, Lei, E-mail: yu-lei@gg.nitto.co.jp [Biomedical Engineering and Technology Institute, Institutes for Advanced Interdisciplinary Research, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062 (China); Biomedical Group, Nitto Denko Technical Corporation, 501 Via Del Monte, Oceanside, CA 92058 (United States); Van, Sang [Biomedical Group, Nitto Denko Technical Corporation, 501 Via Del Monte, Oceanside, CA 92058 (United States)

    2010-12-23

    The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(l-γ-glutamylglutamine)-paclitaxel nano-conjugate (PGG-PTX). PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic.

  3. Design of a controlled release liquid formulation of lamotrigine

    Directory of Open Access Journals (Sweden)

    V Kumar

    2011-05-01

    Full Text Available "n  "n  Background and the purpose of the study: Lamotrigine is a broad spectrum anticonvulsant drug widely used as mono- or adjunct- therapy in adults and children. The aim of this study was to develop controlled release liquid formulation of lamotrigine to improve bioavailability and compliance of pediatric and geriatric epileptic patients. "n  Methods: Multiple (w/o/w emulsion was prepared using one step emulsification technique. It was evaluated for entrapment efficiency (EE, morphology, zeta potential (ZP, polydispersity index (PI, rheology, thermal property, in vitro drug release behavior and stability. In vivo studies in albino mice were carried out using maximal electroshock seizure (MES test and strychnine induced seizure (SIS pattern test and results were compared with marketed formulation. "n  Results: The EE of the formulations varied from 84.37% to 98.11%. The ZP and PI values of the prepared batches were in the range of +23.46 to +28.07 and 0.256 and 0.365, respectively. Microscopic observation clearly indicated the stability of the emulsions during the storage period. All batches exhibited controlled in vitro drug release up to 12 hrs. Batch C11 exhibited significantly longer duration of protection of seizure in mice against MES and exhibited comparable efficacy in SIS as compared to the marketed formulation. "n  Major Conclusion: Multiple emulsion of lamotrigine compared to the marketed tablet showed plasma drug concentration within therapeutic range for longer time and comparable efficacy.

  4. Development of a nanoparticulate formulation of diminazene to treat African trypanosomiasis

    Energy Technology Data Exchange (ETDEWEB)

    Kroubi, Maya; Betbeder, Didier [EA 4483, IFR 114 IMPRT, Faculte de Medecine, Pole recherche, Departement de Physiologie, 1 place de Verdun, 59045 Lille Cedex (France); Daulouede, Sylvie; Mossalayi, Djavad; Vincendeau, Philippe [Laboratoire de Parasitologie, Universite Victor Segalen Bordeaux 2, 146 rue Leo Saignat, 33076 Bordeaux Cedex (France); Karembe, Hamadi [CEVA Sante Animale, ZI la Ballastiere, BP 126, 33501 Libourne (France); Jallouli, Youssef [Faculte de Pharmacie, Universite de Lille 2, 3 rue du Professeur Laguesse, 59006 Lille (France); Howsam, Mike, E-mail: dbetbeder@aol.com [Centre Universitaire de Mesure et d' Analyse, Faculte de Pharmacie, Universite de Lille 2, 3 rue du Professeur Laguesse, 59006 Lille (France)

    2010-12-17

    There is a real need to develop new therapeutic strategies for African trypanosomiasis infections. In our study, we developed a new drug delivery system of diminazene (DMZ), a trypanocidal drug registered for veterinary use. This drug candidate presents a limited efficacy, a poor affinity for brain tissue and instability. The development of colloidal formulations based on a porous cationic nanoparticle with an oily core ({sub 70}DGNP{sup +}), has potentially two advantages: stabilization of the drug and potential targeting of the parasite. We analyzed two processes of drug loading: in process (DMZ was added during the preparation of {sub 70}DGNP{sup +} at 80 deg. C) and post-loading (DMZ was mixed with a {sub 70}DGNP{sup +} solution at room temperature). Poor stability of the drug was observed using the in process technique. When using the post-loading technique over 80% drug entrapment efficiency was obtained at a ratio of DMZ:phospholipids (wt:wt) < 5%. Moreover, DMZ loaded into {sub 70}DGNP{sup +} was found to be protected against oxidation and was stable for at least six months at 4 deg. C. Finally, in vitro tests on T.b. brucei showed an increased efficacy of DMZ loaded in {sub 70}DGNP{sup +}.

  5. Otic drug delivery systems: formulation principles and recent developments.

    Science.gov (United States)

    Liu, Xu; Li, Mingshuang; Smyth, Hugh; Zhang, Feng

    2018-04-25

    Disorders of the ear severely impact the quality of life of millions of people, but the treatment of these disorders is an ongoing, but often overlooked challenge particularly in terms of formulation design and product development. The prevalence of ear disorders has spurred significant efforts to develop new therapeutic agents, but perhaps less innovation has been applied to new drug delivery systems to improve the efficacy of ear disease treatments. This review provides a brief overview of physiology, major diseases, and current therapies used via the otic route of administration. The primary focuses are on the various administration routes and their formulation principles. The article also presents recent advances in otic drug deliveries as well as potential limitations. Otic drug delivery technology will likely evolve in the next decade and more efficient or specific treatments for ear disease will arise from the development of less invasive drug delivery methods, safe and highly controlled drug delivery systems, and biotechnology targeting therapies.

  6. Free energy of hydration of niobium oxide

    International Nuclear Information System (INIS)

    Plodinec, M.J.

    1996-01-01

    Some of the glasses being formulated by SRTC researchers contain niobium oxide. In this report, the free energy of hydration of the oxide is calculated from the free energies of formation of the oxide, the hydroxide, and water. This value can be used in calculations of the free energy of hydration of glasses containing niobium

  7. A multiherbal formulation influencing immune response in vitro.

    Science.gov (United States)

    Menghini, L; Leporini, L; Scanu, N; Pintore, G; Ferrante, C; Recinella, L; Orlando, G; Vacca, M; Brunetti, L

    2012-02-01

    Aim of this study was to evaluate the effects of phytocomplexes of Uncaria, Shiitake and Ribes in terms of viability and inflammatory response on immune cell-derived cultures. Standardized extracts of Uncaria, Shitake and Ribes and their commercial formulation were tested on cell lines PBMC, U937 and macrophage. The activity was evaluated in terms of cell viability (MTT test), variations of oxidative marker release (ROS and PGE2) and modulatory effects on immune response (gene expression of IL-6, IL-8 and TNFα, RT-PCR). Cell viability was not affected by extracts, except subtle variations observed only at higher doses (>250 µg/mL). The extract mixture was well tolerated, with no effects on cell viability up to doses of 500 µg/mL. Pre-treatment of macrophages with subtoxic doses of the extracts reduced the basal release of oxidative markers and enhanced the cell response to exogenous oxidant stimulation, as revealed by ROS and PGE2 release reduction. The same treatment on macrophage resulted in a selective modulation of the immune response, as shown by an increase of IL-6 mRNA and, partially, IL-8 mRNA, while a reduction was observed for TNFα mRNA. Data confirm that extracts and their formulations can act as regulator of the immune system with mechanisms involving the oxidative stress and the release of selected proinflammatory cytokines.

  8. Comparative study of curcumin and curcumin formulated in a solid dispersion: Evaluation of their antigenotoxic effects

    Directory of Open Access Journals (Sweden)

    Leonardo Meneghin Mendonça

    2015-01-01

    Full Text Available AbstractCurcumin (CMN is the principal active component derived from the rhizome of Curcuma longa (Curcuma longa L.. It is a liposoluble polyphenolic compound that possesses great therapeutic potential. Its clinical application is, however, limited by the low concentrations detected following oral administration. One key strategy for improving the solubility and bioavailability of poorly water-soluble drugs is solid dispersion, though it is not known whether this technique might influence the pharmacological effects of CMN. Thus, in this study, we aimed to evaluate the antioxidant and antigenotoxic effects of CMN formulated in a solid dispersion (CMN SD compared to unmodified CMN delivered to Wistar rats. Cisplatin (cDDP was used as the damage-inducing agent in these evaluations. The comet assay results showed that CMN SD was not able to reduce the formation of cDDP-DNA crosslinks, but it decreased the formation of micronuclei induced by cDDP and attenuated cDDP-induced oxidative stress. Furthermore, at a dose of 50 mg/kg b.w. both CMN SD and unmodified CMN increased the expression of Tp53 mRNA. Our results showed that CMN SD did not alter the antigenotoxic effects observed for unmodified CMN and showed effects similar to those of unmodified CMN for all of the parameters evaluated. In conclusion, CMN SD maintained the protective effects of unmodified CMN with the advantage of being chemically water soluble, with maximization of absorption in the gastrointestinal tract. Thus, the optimization of the physical and chemical properties of CMN SD may increase the potential for the therapeutic use of curcumin.

  9. Screening vaccine formulations for biological activity using fresh human whole blood.

    Science.gov (United States)

    Brookes, Roger H; Hakimi, Jalil; Ha, Yukyung; Aboutorabian, Sepideh; Ausar, Salvador F; Hasija, Manvi; Smith, Steven G; Todryk, Stephen M; Dockrell, Hazel M; Rahman, Nausheen

    2014-01-01

    Understanding the relevant biological activity of any pharmaceutical formulation destined for human use is crucial. For vaccine-based formulations, activity must reflect the expected immune response, while for non-vaccine therapeutic agents, such as monoclonal antibodies, a lack of immune response to the formulation is desired. During early formulation development, various biochemical and biophysical characteristics can be monitored in a high-throughput screening (HTS) format. However, it remains impractical and arguably unethical to screen samples in this way for immunological functionality in animal models. Furthermore, data for immunological functionality lag formulation design by months, making it cumbersome to relate back to formulations in real-time. It is also likely that animal testing may not accurately reflect the response in humans. For a more effective formulation screen, a human whole blood (hWB) approach can be used to assess immunological functionality. The functional activity relates directly to the human immune response to a complete formulation (adjuvant/antigen) and includes adjuvant response, antigen response, adjuvant-modulated antigen response, stability, and potentially safety. The following commentary discusses the hWB approach as a valuable new tool to de-risk manufacture, formulation design, and clinical progression.

  10. 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...

  11. Perfume formulation: words and chats.

    Science.gov (United States)

    Ellena, Céline

    2008-06-01

    What does it mean to create fragrances with materials from chemistry and/or from nature? How are they used to display their characteristic differences, their own personality? Is it easier to create with synthetic raw materials or with essential oils? This review explains why a perfume formulation corresponds in fact to a conversation, an interplay between synthetic and natural perfumery materials. A synthetic raw material carries a single information, and usually is very linear. Its smell is uniform, clear, and faithful. Natural raw materials, on the contrary, provide a strong, complex and generous image. While a synthetic material can be seen as a single word, a natural one such as rose oil could be compared to chatting: cold, warm, sticky, heavy, transparent, pepper, green, metallic, smooth, watery, fruity... full of information. Yet, if a very small amount of the natural material is used, nothing happens, the fragrance will not change. However, if a large amount is used, the rose oil will swallow up everything else. The fragrance will smell of nothing else except rose! To formulate a perfume is not to create a culinary recipe, with only dosing the ingredients in well-balanced amounts. To formulate rather means to flexibly knit materials together with a lively stitch, meeting or repelling each other, building a pleasant form, which is neither fixed, nor solid, nor rigid. A fragrance has an overall structure, which ranges from a clear sound, made up of stable, unique, and linear items, to a background chat, comfortable and reassuring. But that does, of course, not mean that there is only one way of creating a fragrance!

  12. Formulation of soy oil products

    Directory of Open Access Journals (Sweden)

    Woerfel, John B.

    1995-12-01

    Full Text Available The paper comments different formulations of soy oil products such as salad and cooking oils, margarine, shortenings, commercial shortenings, frying shortenings, and fluid shortenings. Hydrogenation and its influence on final products is also included.

    El trabajo presenta diferentes formulaciones a base de aceite de soja tales como aceites para ensalada y cocinado, margarina, grasas sólidas (shortenings, grasas sólidas comerciales, grasas sólidas para frituras y grasas fluidas. Hace también referencia al proceso de hidrogenación y a sus efectos en los productos finales.

  13. Formulation and Characterization of Sustained Release Floating ...

    African Journals Online (AJOL)

    Purpose: To formulate sustained release gastroretentive microballoons of metformin hydrochloride with the objective of improving its bioavailability. Methods: Microballoons of metformin hydrochloride were formulated by solvent evaporation and diffusion method using varying mixtures of hydroxypropyl methylcellulose ...

  14. Bioequivalence assessment of two formulations of ibuprofen

    KAUST Repository

    Al-Talla, Zeyad; Akrawi, Sabah H; Tolley, Luke T; Sioud, Salim H; Zaater, Mohammed F; Emwas, Abdul-Hamid M

    2011-01-01

    Background: This study assessed the relative bioavailability of two formulations of ibuprofen. The first formulation was Doloraz , produced by Al-Razi Pharmaceutical Company, Amman, Jordan. The second forumulation was Brufen , manufactured by Boots

  15. Modern approach to relativity theory (radar formulation)

    International Nuclear Information System (INIS)

    Strel'tsov, V.N.

    1991-01-01

    The main peculiarities of the radar formulation of the relativity theory are presented. This formulation operates with the retarded (light) distances and relativistic or radar length introduced on their basis. 21 refs.; 1 tab

  16. Formulation and delivery strategies of ibuprofen: challenges and opportunities.

    Science.gov (United States)

    Irvine, Jake; Afrose, Afrina; Islam, Nazrul

    2018-02-01

    Ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), is mostly administered orally and topically to relieve acute pain and fever. Due to its mode of action this drug may be useful in the treatment regimens of other, more chronic conditions, like cystic fibrosis. This drug is poorly soluble in aqueous media and thus the rate of dissolution from the currently available solid dosage forms is limited. This leads to poor bioavailability at high doses after oral administration, thereby increasing the risk of unwanted adverse effects. The poor solubility is a problem for developing injectable solution dosage forms. Because of its poor skin permeability, it is difficult to obtain an effective therapeutic concentration from topical preparations. This review aims to give a brief insight into the status of ibuprofen dosage forms and their limitations, particle/crystallization technologies for improving formulation strategies as well as suggesting its incorporation into the pulmonary drug delivery systems for achieving better therapeutic action at low dose.

  17. Liquid Secondary Waste Grout Formulation and Waste Form Qualification

    Energy Technology Data Exchange (ETDEWEB)

    Um, Wooyong [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Williams, B. D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Snyder, Michelle M. V. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Wang, Guohui [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2016-05-23

    This report describes the results from liquid secondary waste (LSW) grout formulation and waste form qualification tests performed at Pacific Northwest National Laboratory (PNNL) for Washington River Protection Solutions (WRPS) to evaluate new formulations for preparing a grout waste form with high-sulfate secondary waste simulants and the release of key constituents from these grout monoliths. Specific objectives of the LSW grout formulation and waste form qualification tests described in this report focused on five activities: 1.preparing new formulations for the LSW grout waste form with high-sulfate LSW simulants and solid characterization of the cured LSW grout waste form; 2.conducting the U.S. Environmental Protection Agency (EPA) Method 1313 leach test (EPA 2012) on the grout prepared with the new formulations, which solidify sulfate-rich Hanford Tank Waste Treatment and Immobilization Plant (WTP) off-gas condensate secondary waste simulant, using deionized water (DIW); 3.conducting the EPA Method 1315 leach tests (EPA 2013) on the grout monoliths made with the new dry blend formulations and three LSW simulants (242-A evaporator condensate, Environmental Restoration Disposal Facility (ERDF) leachate, and WTP off-gas condensate) using two leachants, DIW and simulated Hanford Integrated Disposal Facility (IDF) Site vadose zone pore water (VZPW); 4.estimating the 99Tc desorption Kd (distribution coefficient) values for 99Tc transport in oxidizing conditions to support the IDF performance assessment (PA); 5.estimating the solubility of 99Tc(IV)-bearing solid phases for 99Tc transport in reducing conditions to support the IDF PA.

  18. Marketing therapeutic recreation services.

    Science.gov (United States)

    Thorn, B E

    1984-01-01

    The use of marketing strategies can enhance the delivery of therapeutic recreation services. This article discusses how agencies can adapt marketing techniques and use them to identify potential markets, improve image, evaluate external pressures, and maximize internal strengths. Four variables that can be controlled and manipulated in a proposed marketing plan are product, price, place and promotion.

  19. Therapeutic Recombinant Monoclonal Antibodies

    Science.gov (United States)

    Bakhtiar, Ray

    2012-01-01

    During the last two decades, the rapid growth of biotechnology-derived techniques has led to a myriad of therapeutic recombinant monoclonal antibodies with significant clinical benefits. Recombinant monoclonal antibodies can be obtained from a number of natural sources such as animal cell cultures using recombinant DNA engineering. In contrast to…

  20. Therapeutic applications of radiopharmaceuticals

    International Nuclear Information System (INIS)

    Baker, W.J.; Datz, F.L.; Beightol, R.W.

    1987-01-01

    Whether a radiopharmaceutical has diagnostic or therapeutic application depends on both the isotope and pharmaceutical used. For diagnostic applications, the isotope should undergo only γ-decay, since usually only γ-radiation is detected by nuclear medicine cameras. The half-life should be just long enough to allow the procedure to be performed. In contrast, the isotope needed for therapeutic purposes should have particulate radiation, such as a β-particle (electron), since these are locally absorbed an increase the local radiation dose. γ-Radiation, which penetrates the tissues, produces less radiation dose than do Β-particles. Several references dealing with radioactive decay, particulate interactions, and diagnostic and therapeutic applications of radiopharmaceuticals are available. Radiopharmaceuticals can legally be used only by physicians who are qualified by specific training in the safe handling of radionuclides. The experience and training of these physicians must be approved by the Nuclear Regulatory Commission or Agreement State Agency authorized to license the use of radiopharmaceuticals. A list of all byproduct material and procedures is available in the Code of Federal Regulations. Of the many radiopharmaceuticals available for diagnostic and therapeutic use, only those commonly used are discussed in this chapter

  1. Soya, maize, and sorghum-based ready-to-use therapeutic food with amino acid is as efficacious as the standard milk and peanut paste-based formulation for the treatment of severe acute malnutrition in children: a noninferiority individually randomized controlled efficacy clinical trial in Malawi.

    Science.gov (United States)

    Bahwere, Paluku; Akomo, Peter; Mwale, Mwawi; Murakami, Hitoshi; Banda, Chrissy; Kathumba, Sylvester; Banda, Chimwemwe; Jere, Solomon; Sadler, Kate; Collins, Steve

    2017-10-01

    Background: Development of more cost-effective ready-to-use therapeutic food (RUTF) is a global public health priority. To date, previous lower-cost recipes have been less effective than the standard peanut and milk (PM)-based RUTF, particularly in children aged soya, maize, and sorghum (FSMS)-RUTF enriched with crystalline amino acids without cow milk powder and a milk, soya, maize, and sorghum (MSMS)-RUTF containing 9.3% skim cow milk powder. Design: This nonblinded, 3-arm, parallel-group, simple randomized controlled trial enrolled Malawian children with severe acute malnutrition. Results: In intention-to-treat analyses, FSMS-RUTF showed noninferiority for recovery rates in children aged 24-59 mo (Δ: -1.9%; 95% CI: -9.5%, 5.6%) and 6-23 mo (Δ: -0.2%; 95% CI: -7.5%, 7.1%) compared with PM-RUTF. MSMS-RUTF also showed noninferiority for recovery rates in children aged 24-59 mo (Δ: 0.0%; 95% CI: -7.3%, 7.4%) and 6-23 mo (Δ: 0.6%; 95% CI: -4.3%, 5.5%). Noninferiority in recovery rates was also observed in per-protocol analyses. For length of stay in the program (time to cure), both FSMS-RUTF in children aged 24-59 mo (Δ: 2.8 d; 95% CI: -0.8, 6.5 d) and 6-23 mo (Δ: 3.4 d; 95% CI: -1.2, 8.0 d) and MSMS-RUTF in children aged 24-59 mo (Δ: 0.2 d; 95% CI: -3.1, 3.6 d) and 6-23 mo (Δ: 1.2 d; 95% CI: -3.4, 5.8 d) were not inferior to PM-RUTF. FSMS-RUTF was also significantly better than PM-RUTF at increasing hemoglobin and body iron stores in anemic children, with mean hemoglobin increases of 2.1 (95% CI: 1.6, 2.6) and 1.3 (95% CI: 0.9, 1.8) and mean body iron store increases of 2.0 (95% CI: 0.8, 3.3) and 0.1 (95% CI: -1.1, 1.3) for FSMS-RUTF and PM-RUTF, respectively. Conclusions: FSMS-RUTF without milk is efficacious in the treatment of severe acute malnutrition in children aged 6-23 and 24-59 mo. It is also better at correcting iron deficiency anemia than PM-RUTF. This trial was registered at www.pactr.org as PACTR201505001101224. © 2017 American Society for

  2. Formulation, Preparation, and Characterization of Polyurethane Foams

    Science.gov (United States)

    Pinto, Moises L.

    2010-01-01

    Preparation of laboratory-scale polyurethane foams is described with formulations that are easy to implement in experiments for undergraduate students. Particular attention is given to formulation aspects that are based on the main chemical reactions occurring in polyurethane production. This allows students to develop alternative formulations to…

  3. Performance Evaluation of Abrasive Grinding Wheel Formulated ...

    African Journals Online (AJOL)

    This paper presents a study on the formulation and manufacture of abrasive grinding wheel using locally formulated silicon carbide abrasive grains. Six local raw material substitutes were identified through pilot study and with the initial mix of the identified materials, a systematic search for an optimal formulation of silicon ...

  4. Optimization of chlorphenesin emulgel formulation.

    Science.gov (United States)

    Mohamed, Magdy I

    2004-10-11

    This study was conducted to develop an emulgel formulation of chlorphenesin (CHL) using 2 types of gelling agents: hydroxypropylmethyl cellulose (HPMC) and Carbopol 934. The influence of the type of the gelling agent and the concentration of both the oil phase and emulsifying agent on the drug release from the prepared emulgels was investigated using a 2(3) factorial design. The prepared emulgels were evaluated for their physical appearance, rheological behavior, drug release, antifungal activity, and stability. Commercially available CHL topical powder was used for comparison. All the prepared emulgels showed acceptable physical properties concerning color, homogeneity, consistency, spreadability, and pH value. They also exhibited higher drug release and antifungal activity than the CHL powder. It was found that the emulsifying agent concentration had the most pronounced effect on the drug release from the emulgels followed by the oil phase concentration and finally the type of the gelling agent. The drug release from all the emulgels was found to follow diffusion-controlled mechanism. Rheological studies revealed that the CHL emulgels exhibited a shear-thinning behavior with thixotropy. Stability studies showed that the physical appearance, rheological properties, drug release, and antifungal activity in all the prepared emulgels remained unchanged upon storage for 3 months. As a general conclusion, it was suggested that the CHL emulgel formulation prepared with HPMC with the oil phase concentration in its low level and emulsifying agent concentration in its high level was the formula of choice since it showed the highest drug release and antifungal activity.

  5. High-throughput oxidation screen of antibody-drug conjugates by analytical protein A chromatography following IdeS digest.

    Science.gov (United States)

    Buecheler, Jakob W; Winzer, Matthias; Weber, Christian; Gieseler, Henning

    2018-05-01

    Oxidation of protein therapeutics is a major chemical degradation pathway which may impact bioactivity, serum half-life and stability. Therefore, oxidation is a relevant parameter which has to be monitored throughout formulation development. Methods such as HIC, RPLC and LC/MS achieve a separation of oxidized and non-oxidized species by differences in hydrophobicity. Antibody-drug conjugates (ADC) although are highly more complex due to the heterogeneity in linker, drug, drug-to-antibody ratio (DAR) and conjugation site. The analytical protein A chromatography can provide a simple and fast alternative to these common methods. A miniature analytical protein A chromatography method in combination with an IdeS digest was developed to analyse ADCs. The IdeS digest efficiency of an IgG1 was monitored using SEC-HPLC and non-reducing SDS-PAGE. An antibody-fluorescent dye conjugate was conjugated at different dye-to-antibody ratios as model construct to mimic an ADC. With IdeS, an almost complete digest of a model IgG1 can be achieved (digested protein amount >98%). This enables subsequent analytical protein A chromatography, which consequently eliminates any interference of payload with the stationary phase. A novel high-throughput method for an interchain cysteine-linked ADC oxidation screens during formulation development was developed. © 2018 Royal Pharmaceutical Society.

  6. Preformulation and formulation development of a bioactive nitroaromatic compound

    Science.gov (United States)

    Sena, Camila F. A.; Apolinário, Lívia S.; Duarte, Jaqueline A.; dos Santos, Giovanna C.; Monteiro, Liziane O. F.; de Oliveira, Mônica C.; Leite, Elaine A.; de Oliveira, Renata B.

    2017-11-01

    The N-(butanoyloxyethyl)-4-(chloromethyl)-3-nitrobenzamide (BNB) is a nitroaromatic derivative with significant antitumor activity. Preformulation, forced degradation (distilled water, acid and base hydrolysis, oxidation, and light), and formulation studies were performed to investigate the chemical behavior of the molecule, the physicochemical properties, and the impact of formulation variables. Pharmacokinetic properties for BNB were estimated in silico. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) containing BNB were developed by a hot melt homogenization method for parenteral administration. Degradation studies demonstrated that this compound is sensitive to hydrolysis. BNB was predicted to have a favorable absorption, distribution, metabolism, and excretion profile. The nanocarriers developed were characterized for particle size (PS = 61 to 85 nm), polydispersity index (PI moderate cytotoxicity against breast cancer cell line. Blank formulations did not induce cytotoxicity and BNB-loaded SLN was able to potentiate the action of BNB (lC50 12.4 μM). BNB is a promising antitumor agent and it is possible to modulate its activity based on the particle size of the formulation.

  7. New formulations of ready-to-use foods

    International Nuclear Information System (INIS)

    Dibari, Filippo; Akomo, Peter; Collins, Steve; Bahwere, Paluku

    2014-01-01

    Development of improved Ready-to-Use Therapeutic Foods (RUTFs) is a priority since the endorsement of the Community-based Management of Acute Malnutrition (CMAM). The most commonly used formulation is based on peanut and milk powder, but the following issues need to be addressed: acceptability is low in certain cultural contexts; milk powder is very expensive (about 50% of the total ingredient cost) and therefore it constraints the scaling up of local/regional production; peanut are often prone to aflatoxin contamination. Therefore, Valid International developed and trialled alternative RUTF formulations based on locally available and/or cheaper ingredients: Chickpea- and Sesame-based RUTF (CS-RUTF), Soya-, Maize, Sorghum-based RUTF (SMS-RUTF), and Whey Protein-based RUTF (WPC-RUTF). In Malawi, an observational study highlighted that CS-RUTF was effective in reversing HIV wasting in adults, and bio-electrical impedance measurements suggested a positive direct correlation between weight gain and free fat mass. In the same country, a randomized controlled trial demonstrated that WPC-RUTF was not inferior to the standard peanut and milk-based formulation (P-RUTF) when rehabilitating children under five years of age from severe acute malnutrition (SAM). In other two similar studies conducted in Zambia and Democratic Republic of Congo, SMS-RUTF and P-RUTF were equivalently efficient in rehabilitating SAM in children aged 2 to 5 years, but not in those below 2 years. In this presentation, we will (i) describe the procedures used for the development of the RUTF formulations, (ii) share successes and challenges encountered in formulating lower cost prototypes that meet international standards, (iii) suggest ways to reduce effect of anti-nutrients, to enhance bioavailability of crucial micronutrients (e.g. iron), and minimize abdominal discomfort. Based on results from efficacy and effectiveness trials, we will discuss their implications for policy-making and implementation

  8. El estrés oxidativo como mecanismo de acción del plomo: Implicancias terapéuticas Oxidative stress as a mechanism of action of lead: Therapeutic implications

    Directory of Open Access Journals (Sweden)

    Samanta Andrea Martínez

    2011-12-01

    Full Text Available El plomo (Pb es un metal no esencial altamente tóxico que afecta a diversos órganos y tejidos. Si bien aún no ha sido descripto un mecanismo único mediante el cual este metal ejerce sus efectos tóxicos, un gran número de estudios han puesto en evidencia el rol fundamental del estrés oxidativo en la intoxicación por Pb. A este respecto, ha sido informado que en la intoxicación por Pb el estrés oxidativo puede ocurrir a diferentes niveles: por generación de ácido ä-aminolevulínico (ä-ALA, por la capacidad per se que posee el Pb para inducir peroxidación lipídica en presencia de ión ferroso (Fe2+, o por depleción de glutatión (GSH y enzimas antioxidantes. Sobre la base de estos antecedentes, el objetivo de esta revisión es presentar evidencias recientes sobre la implicancia del estrés oxidativo en los efectos adversos ocasionados por Pb, destacar la posibilidad de utilización de biomarcadores de estrés oxidativo como un método complementario al diagnóstico temprano de exposición y revelar la importancia de los compuestos antioxidantes como nuevas herramientas en la prevención y tratamiento de la intoxicación por este metal.Lead (Pb is a highly toxic non-essential metal that affects different organs and tissues. Although at the present a unique mechanism by which this metal exerts its toxic effects has not been described, a large number of studies have highlighted the fundamental role of oxidative stress in the pathophysiology of Pb poisoning. In this regard, it has been reported that Pb-induced oxidative stress can occur at different levels: by the generation of ä-aminolevulinic acid (ä-ALA, through its ability to induce lipid peroxidation in the presence of ferrous ion (Fe2+, or via glutathione (GSH or antioxidant enzyme depletion. On the basis of these antecedents, the aim of this review is to present recent evidence regarding the implication of oxidative stress in the adverse effects caused by Pb, to emphasize the

  9. Formulation development for PREPP concreted waste forms

    International Nuclear Information System (INIS)

    Neilson, R.M. Jr.; Welch, J.M.

    1984-05-01

    Analysis of variance and logistic regression techniques have been used to develop models describing the effects of formulation variables and their interactions on compressive strength, solidification, free-standing water, and workability of hydraulic cement grouts incorporating simulated Process Experimental Pilot Plant (PREPP) wastes. These models provide the basis for specifications of grout formulations to solidify these wastes. The experimental test matrix, formulation preparation, and test methods employed are described. The development of analytical models for formulation behavior and the conclusions drawn regarding appropriate formulation variable ranges are discussed. 13 references, 9 figures, 15 tables

  10. Radical scavenging potentials of single and combinatorial herbal formulations in vitro

    Directory of Open Access Journals (Sweden)

    Okey A. Ojiako

    2016-04-01

    Full Text Available Reactive oxygen and nitrogen species (RONS are involved in deleterious/beneficial biological processes. The present study sought to investigate the capacity of single and combinatorial herbal formulations of Acanthus montanus, Emilia coccinea, Hibiscus rosasinensis, and Asystasia gangetica to act as superoxide radicals (SOR, hydrogen peroxide (HP, nitric oxide radical (NOR, hydroxyl radical (HR, and 2,2-diphenyl-1-picrylhydrazyl (DPPH radical antagonists using in vitro models. The herbal extracts were single herbal formulations (SHfs, double herbal formulations (DHfs, triple herbal formulations (THfs, and a quadruple herbal formulation (QHf. The phytochemical composition and radical scavenging capacity index (SCI of the herbal formulations were measured using standard methods. The flavonoids were the most abundant phytochemicals present in the herbal extracts. The SCI50 defined the concentration (μg/mL of herbal formulation required to scavenge 50% of the investigated radicals. The SHfs, DHfs, THfs, and QHf SCI50 against the radicals followed the order HR > SOR > DPPH radical > HP > NOR. Although the various herbal formulations exhibited ambivalent antioxidant activities in terms of their radical scavenging capabilities, a broad survey of the results of the present study showed that combinatorial herbal formulations (DHfs, THfs, and QHf appeared to exhibit lower radical scavenging capacities than those of the SHfs in vitro.

  11. Understanding effect of formulation and manufacturing variables on the critical quality attributes of warfarin sodium product.

    Science.gov (United States)

    Rahman, Ziyaur; Korang-Yeboah, Maxwell; Siddiqui, Akhtar; Mohammad, Adil; Khan, Mansoor A

    2015-11-10

    Warfarin sodium (WS) is a narrow therapeutic index drug and its product quality should be thoroughly understood and monitored in order to avoid clinical performance issues. This study was focused on understanding the effect of manufacturing and formulation variables on WS product critical quality attributes (CQAs). Eight formulations were developed with lactose monohydrate (LM) or lactose anhydrous (LA), and were either wet granulated or directly compressed. Formulations were granulated either with ethanol, isopropyl alcohol (IPA) and IPA-water mixture (50:50). Formulations were characterized for IPA, water content, hardness, disintegration time (DT), assay, dissolution and drug physical forms (scanning electron microscopy (SEM), near infrared chemical imaging (NIR-CI), X-ray powder diffraction (XRPD) and solid state nuclear magnetic resonance (ssNMR)), and performed accelerated stability studies at 40°C/75% RH for three days. The DT and dissolution of directly compressed formulations were faster than wet granulated formulations. This was due to phase transformation of crystalline drug into its amorphous form as indicated by SEM, NIR-CI, XRPD and ssNMR data which itself act as a binder. Similarly, LM showed faster disintegration and dissolution than LA containing formulations. Stability results indicated an increase in hardness and DT, and a decrease in dissolution rate and extent. This was due to phase transformation of the drug and consolidation with particles' bonding. In conclusion, the CQAs of WS product were significantly affected by manufacturing and formulation variables. Published by Elsevier B.V.

  12. Energy policy formulation for Pakistan

    International Nuclear Information System (INIS)

    Riaz, T.

    1981-01-01

    Pakistan is a low income, low energy consumption country. In view of the close interdependence between economic growth and energy consumption, she will need increasing energy supplies in order to maintain her economic growth. This paper develops an energy sector optimization model for the Pakistan economy, which consists of production models for five energy industries, ie oil, gas, coal, electricity (including electricity generated in nuclear power plants) and non-commercial fuels. The model is first used to forecast energy balances for the period 1975 - 2006. The model is then employed to formulate a long-term comprehensive energy policy for Pakistan. Finally the suggested policy is compared with the current official energy programme. (author)

  13. On Scalar Energy: Mathematical Formulation

    International Nuclear Information System (INIS)

    Hathout, A.M.

    2011-01-01

    A new kind of electromagnetic waves (EMW), which exists only in vacuum of the empty space, will be discussed and mathematically formulated in this paper. The mathematical existence of this energy was first proposed in a series of groundbreaking equations by Scottish Mathematician, James Clerk Maxwell, in the mid of 1800 and 39;s. This energy is called scalar energy. It is characterized by both particle and wave like. The waves of this energy are called longitudinal EMW to distinguish them from transverse EM, the kind we are familiar with in our daily life. Teslas name of this energy is scalar energy or zero point energy. It is aimed at this paper to explain more details and to verify the scalar EM concept in vacuum.

  14. Curcumin and its topical formulations for wound healing applications.

    Science.gov (United States)

    Mohanty, Chandana; Sahoo, Sanjeeb K

    2017-10-01

    Oxidative damage and inflammation have been identified, through clinical and preclinical studies, as the main causes of nonhealing chronic wounds. Reduction of persistent chronic inflammation by application of antioxidant and anti-inflammatory agents such as curcumin has been well studied. However, low aqueous solubility, poor tissue absorption, rapid metabolism and short plasma half-life have made curcumin unsuitable for systemic administration for better wound healing. Recently, various topical formulations of curcumin such as films, fibers, emulsion, hydrogels and different nanoformulations have been developed for targeted delivery of curcumin at wounded sites. In this review, we summarize and discuss different topical formulations of curcumin with emphasis on their wound-healing properties in animal models. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Glass formulation for phase 1 high-level waste vitrification

    International Nuclear Information System (INIS)

    Vienna, J.D.; Hrma, P.R.

    1996-04-01

    The purpose of this study is to provide potential glass formulations for prospective Phase 1 High-Level Waste (HLW) vitrification at Hanford. The results reported here will be used to aid in developing a Phase 1 HLW vitrification request for proposal (RFP) and facilitate the evaluation of ensuing proposals. The following factors were considered in the glass formulation effort: impact on total glass volume of requiring the vendor to process each of the tank compositions independently versus as a blend; effects of imposing typical values of B 2 O 3 content and waste loading in HLW borosilicate glasses as restrictions on the vendors (according to WAPS 1995, the typical values are 5--10 wt% B 2 O 3 and 20--40 wt% waste oxide loading); impacts of restricting the processing temperature to 1,150 C on eventual glass volume; and effects of caustic washing on any of the selected tank wastes relative to glass volume

  16. Surfactant mediated slurry formulations for Ge CMP applications

    KAUST Repository

    Basim, G. Bahar

    2013-01-01

    In this study, slurry formulations in the presence of self-assembled surfactant structures were investigated for Ge/SiO2 CMP applications in the absence and presence of oxidizers. Both anionic (sodium dodecyl sulfate-SDS) and cationic (cetyl trimethyl ammonium bromide-C12TAB) micelles were used in the slurry formulations as a function of pH and oxidizer concentration. CMP performances of Ge and SiO2 wafers were evaluated in terms of material removal rates, selectivity and surface quality. The material removal rate responses were also assessed through AFM wear rate tests to obtain a faster response for preliminary analyses. The surfactant adsorption characteristics were studied through surface wettability responses of the Ge and SiO2 wafers through contact angle measurements. It was observed that the self-assembled surfactant structures can help obtain selectivity on the silica/germanium system at low concentrations of the oxidizer in the slurry. © 2013 Materials Research Society.

  17. PYTHIOSIS: A THERAPEUTIC APPROACH

    Directory of Open Access Journals (Sweden)

    C. M. C. Falcão

    2015-10-01

    Full Text Available Pythiosis, a disease caused by the oomycete Pythium insidiosum, often presents inefficient response to chemotherapy. It is a consensus that, in spite the several therapeutic protocols, a combination of surgery, chemotherapy and immunotherapy should be used. Surgical excision requires the removal of the entire affected area, with a wide margin of safety. The use of antifungal drugs has resulted in variable results, both in vitro and in vivo, and presents low therapeutic efficiency due to differences in the agent characteristics, which differ from true fungi. Immunotherapy is a non-invasive alternative for the treatment of pythiosis, which aims at modifying the immune response of the host, thereby producing an effective response to the agent. Photodynamic therapy has emerged as a promising technique, with good activity against P. insidiosum in vitro and in vivo. However, more studies are necessary to increase the efficiency of the current treatment protocols and consequently improve the cure rates. This paper aims to conduct a review covering the conventional and recent therapeutic methods against P. insidiosum infections

  18. A novel nanoparticle formulation for sustained paclitaxel delivery.

    Science.gov (United States)

    Trickler, W J; Nagvekar, A A; Dash, A K

    2008-01-01

    To develop a novel nanoparticle drug delivery system consisting of chitosan and glyceryl monooleate (GMO) for the delivery of a wide variety of therapeutics including paclitaxel. Chitosan/GMO nanoparticles were prepared by multiple emulsion (o/w/o) solvent evaporation methods. Particle size and surface charge were determined. The morphological characteristics and cellular adhesion were evaluated with surface or transmission electron microscopy methods. The drug loading, encapsulation efficiency, in vitro release and cellular uptake were determined using HPLC methods. The safety and efficacy were evaluated by MTT cytotoxicity assay in human breast cancer cells (MDA-MB-231). These studies provide conceptual proof that chitosan/GMO can form polycationic nano-sized particles (400 to 700 nm). The formulation demonstrates high yields (98 to 100%) and similar entrapment efficiencies. The lyophilized powder can be stored and easily be resuspended in an aqueous matrix. The nanoparticles have a hydrophobic inner-core with a hydrophilic coating that exhibits a significant positive charge and sustained release characteristics. This novel nanoparticle formulation shows evidence of mucoadhesive properties; a fourfold increased cellular uptake and a 1000-fold reduction in the IC(50) of PTX. These advantages allow lower doses of PTX to achieve a therapeutic effect, thus presumably minimizing the adverse side effects.

  19. Synergistic antioxidant action of vitamin E and rutin SNEDDS in ameliorating oxidative stress in a Parkinson's disease model.

    Science.gov (United States)

    Sharma, Shrestha; Narang, Jasjeet K; Ali, Javed; Baboota, Sanjula

    2016-09-16

    Oxidative stress is the leading cause in the pathogenesis of Parkinson's disease. Rutin is a naturally occurring strong antioxidant molecule with wide therapeutic applications. It suffers from the problem of low oral bioavailability which is due to its poor aqueous solubility. In order to increase the solubility self-nanoemulsifying drug delivery systems (SNEDDS) of rutin were prepared. The oil, surfactant and co-surfactant were selected based on solubility/miscibility studies. Optimization was done by a three-factor, four-level (34) Box-Behnken design. The independent factors were oil, surfactant and co-surfactant concentration and the dependent variables were globule size, self-emulsification time, % transmittance and cumulative percentage of drug release. The optimized SNEDDS formulation (RSE6) was evaluated for various release studies. Antioxidant activity was assessed by various in vitro tests such as 2,2-diphenyl-1-picrylhydrazyl and reducing power assay. Oxidative stress models which had Parkinson's-type symptoms were used to determine the antioxidant potential of rutin SNEDDS in vivo. Permeation was assessed through confocal laser scanning microscopy. An optimized SNEDDS formulation consisting of Sefsol + vitamin E-Solutol HS 15-Transcutol P at proportions of 25:35:17.5 (w/w) was prepared and characterized. The globule size and polydispersity index of the optimized formulation was found to be 16.08 ± 0.02 nm and 0.124 ± 0.01, respectively. A significant (p < 0.05) increase in the percentage of drug release was achieved in the case of the optimized formulation as compared to rutin suspension. Pharmacokinetic study showed a 2.3-fold increase in relative oral bioavailability. The optimized formulation had significant in vitro and in vivo antioxidant activity. Rutin SNEDDS have been successfully prepared and they can serve as an effective tool in enhancing the oral bioavailability and efficacy of rutin, thus helping in ameliorating oxidative stress in

  20. Prospects for therapeutic mitochondrial transplantation.

    Science.gov (United States)

    Gollihue, Jenna L; Rabchevsky, Alexander G

    2017-07-01

    Mitochondrial dysfunction has been implicated in a multitude of diseases and pathological conditions- the organelles that are essential for life can also be major players in contributing to cell death and disease. Because mitochondria are so well established in our existence, being present in all cell types except for red blood cells and having the responsibility of providing most of our energy needs for survival, then dysfunctional mitochondria can elicit devastating cellular pathologies that can be widespread across the entire organism. As such, the field of "mitochondrial medicine" is emerging in which disease states are being targeted therapeutically at the level of the mitochondrion, including specific antioxidants, bioenergetic substrate additions, and membrane uncoupling agents. New and compelling research investigating novel techniques for mitochondrial transplantation to replace damaged or dysfunctional mitochondria with exogenous healthy mitochondria has shown promising results, including tissue sparing accompanied by increased energy production and decreased oxidative damage. Various experimental techniques have been attempted and each has been challenged to accomplish successful transplantation. The purpose of this review is to present the history of mitochondrial transplantation, the different techniques used for both in vitro and in vivo delivery, along with caveats and pitfalls that have been discovered along the way. Results from such pioneering studies are promising and could be the next big wave of "mitochondrial medicine" once technical hurdles are overcome. Copyright © 2017 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

  1. Formulation and Characterization of ADN-Based Liquid Monopropellants

    Science.gov (United States)

    Wingborg, N.; Eldsäter, C.; Skifs, H.

    2004-10-01

    Ternary ionic solutions are promising green propellants to replace monopropellant hydrazine. Ammonium dinitramide, ADN, is well suited as oxidizer in these propellants due to its high solubility. This paper presents the formulation of different ADN-based liquid monopropellants and the characterization of their properties such as stability, density, viscosity and sensitivity. To be able to use ADN-based monopropellants for propulsion applications, ADN must be produced in a way to minimize the effect on the environment and in sufficient quantities. This paper thus also briefly presents the industrial production of ADN in Sweden and the efforts made to optimize the process.

  2. Augmentation of therapeutic potential of curcumin using nanotechnology: current perspectives.

    Science.gov (United States)

    Sivasami, Pulavendran; Hemalatha, Thiagarajan

    2018-02-28

    Curcumin, an active principle of Curcuma longa, is extracted from the rhizome. Its therapeutic efficiency has been proved using various in vitro and in vivo models. Inflammatory, neoplastic and preneoplastic diseases are the major targets using curcumin as therapeutic agent. Feasible clinical formulations could not be obtained because of its lack of solubility, stability and higher degradation rate. Recently, many techniques have been evolved to improve the physicochemical properties of pharmacological compounds, thereby increasing their biological activity. Curcumin has been developed using various techniques, particularly micro and nanotechnology to improve its stability and bioavailability. This review focuses on the studies pertaining to the delivery of curcumin in the form of micro and nanosize formulations for the treatment of a variety of diseases.

  3. Nitrate and nitrite in biology, nutrition and therapeutics

    Science.gov (United States)

    Lundberg, Jon O.; Gladwin, Mark T.; Ahluwalia, Amrita; Benjamin, Nigel; Bryan, Nathan S.; Butler, Anthony; Cabrales, Pedro; Fago, Angela; Feelisch, Martin; Ford, Peter C.; Freeman, Bruce A.; Frenneau, Michael; Friedman, Joel; Kelm, Malte; Kevil, Christopher G.; Kim-Shapiro, Daniel B.; Kozlov, Andrey V.; Lancaster, Jack R.; Lefer, David J.; McColl, Kenneth; McCurry, Kenneth; Patel, Rakesh; Petersson, Joel; Rassaf, Tienush; Reutov, Valentin P.; Richter-Addo, George B.; Schechter, Alan; Shiva, Sruti; Tsuchiya, Koichiro; van Faassen, Ernst E.; Webb, Andrew J.; Zuckerbraun, Brian S.; Zweier, Jay L.; Weitzberg, Eddie

    2014-01-01

    Inorganic nitrate and nitrite from endogenous or dietary sources are metabolized in vivo to nitric oxide (NO) and other bioactive nitrogen oxides. The nitrate-nitrite-NO pathway is emerging as an important mediator of blood flow regulation, cell signaling, energetics and tissue responses to hypoxia. The latest advances in our understanding of the biochemistry, physiology and therapeutics of nitrate, nitrite and NO were discussed during a recent two-day meeting at the Nobel Forum, Karolinska Institutet in Stockholm. PMID:19915529

  4. Colour and spreadability of Neem (Azadirachta Indica A. juss) ointment and cream formulations

    Science.gov (United States)

    Zawiyyah, Azierah; Shamsul Anuar, Mohd

    2018-04-01

    Herbal plants are a major source of raw material for traditional medicines. Recently there has been an increase of interest to study the therapeutic potential of herbal plants as herbal care products. In this study, a preliminary study on the formulation of neem (Azadirachta Indica) ointment and cream have been conducted. The neem leaves were extracted and formulated into ointment and cream. The raw neem extract is added into the ointment and cream bases at four different concentrations (0% w/w, 0.5% w/w, 1% w/w and 2% w/w) and stored at three different storage temperatures (4°C, 25°C and 45°C). The semambu ointment and cream formulated were evaluated in terms of their colour and spreadability. It has been found that the extract content and storage temperature influence the colour and spreadability of the formulated neem ointment and cream.

  5. Stroke and Therapeutic Hypothermia

    Directory of Open Access Journals (Sweden)

    Ozlem Ozkan Kuscu

    2016-09-01

    Full Text Available Stroke is significant cause of morbidity and mortality caused by disruption of blood flow. Neural injury occurs with two stage; while primary neural injury occurs with disruption of blood flow, after days and hours with metabolic processes secondary injury develops in tissues which is non injured in the first stage. Therefore it is important to prevent and treat the secondary injury as much as preventing and treating the primary neural injury. In this article developing pathophysiological changes after stroke, mechanisms of therapeutic hypothermia, application methods, the factors that determine the effectiveness, side effects and complications were reviewed. [Archives Medical Review Journal 2016; 25(3.000: 351-368

  6. Slag-based saltstone formulations

    International Nuclear Information System (INIS)

    Langton, C.A.

    1987-01-01

    Approximately 400 x 10 6 liters of low-level alkaline salt solution will be treated at the Savannah River Plant (SRP) Defense Waste Processing Facility (DWPF) prior to disposal in concrete vaults at SRP. Treatment involves removal of CS + and Sr +2 followed by solidification and stabilization of potential contaminants in saltstone, a hydrated ceramic waste form. Chromium, technetium, and nitrate releases from saltstone can be significantly reduced by substituting hydraulic blast furnace slag for portland cement in the formulation designs. Slag-based mixes are also compatible with Class F fly ash used in saltstone as a functional extender to control heat of hydration and reduce permeability. A monolithic waste form is produced by the hydration of the slag and fly ash. Soluble ion release (NO 3 - ) is controlled by the saltstone microstructure. Chromium and technetium are less leachable from slag mixes compared to cement-based waste forms because these species are chemically reduced to a lower valence state by ferrous iron in the slag and precipitated as relatively insoluble phases, such as CR(OH) 3 and TcO 2 . 5 refs., 4 figs., 4 tabs

  7. Slag-based saltstone formulations

    International Nuclear Information System (INIS)

    Langton, C.A.

    1987-08-01

    Approximately 400 x 10 6 L of low-level alkaline salt solution will be treated at the Savannah River Plant (SRP) Defense Waste Processing Facility (DWPF) prior to disposal in concrete vaults at SRP. Treatment involves removal of Cs + and Sr +2 , followed by solidification and stabilization of potential contaminants in saltstone, a hydrated ceramic wasteform. Chromium, technetium, and nitrate releases from saltstone can be significantly reduced by substituting hydraulic blast furnace slag for portland cement in the formulation designs. Slag-based mixes are also compatible with the Class F flyash used in saltstone as a functional extender to control heat of hydration and reduce permeability. (Class F flyash is also locally available at SRP.) A monolithic wasteform is produced by the hydration of the slag and flyash. Soluble ion release (NO 3- ) is controlled by the saltstone microstructure. Chromium and technetium are less leachable from slag mixes because these species are chemically reduced to a lower valence state by ferrous iron in the slag and are precipitated as relatively insoluble phases, such as Cr(OH) 3 and TcO 2 . 3 refs., 3 figs., 2 tabs

  8. Policy formulation of public acceptance

    International Nuclear Information System (INIS)

    Kasai, Akihiro

    1978-01-01

    Since 1970, the new policy formulation for public acceptance of the new consideration on the location of electric power generation has been set and applied. The planning and the enforcement being conducted by local public organizations for the local economic build-up with plant location and also the adjustement of the requirements for fishery are two main specific characters in this new policy. The background of this new public acceptance policy, the history and the actual problems about the compensation for the location of power generation plants are reviewed. One new proposal, being recommended by the Policy and Science Laboratory to MITI in 1977 is explained. This is based on the method of promoting the location of power generation plants by public participation placing the redevelopment of regional societies as its basis. The problems concerning the industrial structures in farm villages, fishing villages and the areas of commerce and industry should be systematized, and explained from the viewpoint of outside impact, the characteristics of local areas and the location problems in this new proposal. Finally, the location process and its effectiveness should be put in order. (Nakai, Y.)

  9. Hamiltonian formulation of reduced magnetohydrodynamics

    International Nuclear Information System (INIS)

    Morrison, P.J.; Hazeltine, R.D.

    1983-07-01

    Reduced magnetohydrodynamics (RMHD) has become a principal tool for understanding nonlinear processes, including disruptions, in tokamak plasmas. Although analytical studies of RMHD turbulence have been useful, the model's impressive ability to simulate tokamak fluid behavior has been revealed primarily by numerical solution. The present work describes a new analytical approach, not restricted to turbulent regimes, based on Hamiltonian field theory. It is shown that the nonlinear (ideal) RMHD system, in both its high-beta and low-beta versions, can be expressed in Hanmiltonian form. Thus a Poisson bracket, [ , ], is constructed such that each RMHD field quantitity, xi/sub i/, evolves according to xi/sub i/ = [xi/sub i/,H], where H is the total field energy. The new formulation makes RMHD accessible to the methodology of Hamiltonian mechanics; it has lead, in particular, to the recognition of new RMHD invariants and even exact, nonlinear RMHD solutions. A canonical version of the Poisson bracket, which requires the introduction of additional fields, leads to a nonlinear variational principle for time-dependent RMHD

  10. Formulation of disperse systems science and technology

    CERN Document Server

    Tadros, Tharwat F

    2014-01-01

    This book presents comprehensively the science and technology behind the formulation of disperse systems like emulsions, suspensions, foams and others. Starting with a general introduction, the book covers a broad range of topics like the role of different classes of surfactants, stability of disperse systems, formulation of different dispersions, evaluation of formulations and many more. Many examples are included, too. Written by the experienced author and editor Tharwart Tadros, this book is indispensable for every scientist working in the field.

  11. Formulated arthropod cadavers for pest suppression

    OpenAIRE

    2001-01-01

    Pesticidal and/or antimicrobial biological agent-infected arthropod cadavers are formulated by applying a coating agent once on the surface of the cadaver which either (a) prevents the cadavers from sticking together and/or rupturing or (b) acts as an adhesive for a powder or granule applied to the cadaver to prevent sticking and rupturing. The formulated cadavers maintain or improve infectivity, reproducibility, and survivability. The formulated cadavers can be partially desiccated to improv...

  12. Multiple excitation of supports - Part 1. Formulation

    International Nuclear Information System (INIS)

    Galeao, A.C.N.R.; Barbosa, H.J.C.

    1980-12-01

    The formulation and the solution of a simple specific problem of support movement are presented. The formulation is extended to the general case of infinitesimal elasticity where the approximated solutions are obtained by the variational formulation with spatial discretization by Finite Element Method. Finally, the present usual numerical techniques for the treatment of the resulting ordinary differential equations system are discused: Direct integration, Modal overlap, Spectral response. (E.G.) [pt

  13. A Corrected Formulation of the Multilayer Model (MLM) for Inferring Gaseous Dry Deposition to Vegetated Surfaces

    Science.gov (United States)

    Saylor, Rick D.; Wolfe, Glenn M.; Meyers, Tilden P.; Hicks, Bruce B.

    2014-01-01

    The Multilayer Model (MLM) has been used for many years to infer dry deposition fluxes from measured trace species concentrations and standard meteorological measurements for national networks in the U.S., including the U.S. Environmental Protection Agency's Clean Air Status and Trends Network (CASTNet). MLM utilizes a resistance analogy to calculate deposition velocities appropriate for whole vegetative canopies, while employing a multilayer integration to account for vertically varying meteorology, canopy morphology and radiative transfer within the canopy. However, the MLM formulation, as it was originally presented and as it has been subsequently employed, contains a non-physical representation related to the leaf-level quasi-laminar boundary layer resistance that affects the calculation of the total canopy resistance. In this note, the non-physical representation of the canopy resistance as originally formulated in MLM is discussed and a revised, physically consistent, formulation is suggested as a replacement. The revised canopy resistance formulation reduces estimates of HNO3 deposition velocities by as much as 38% during mid-day as compared to values generated by the original formulation. Inferred deposition velocities for SO2 and O3 are not significantly altered by the change in formulation (less than 3%). Inferred deposition loadings of oxidized and total nitrogen from CASTNet data may be reduced by 10-20% and 5-10%, respectively, for the Eastern U. S. when employing the revised formulation of MLM as compared to the original formulation.

  14. Superspace formulation of new nonlinear sigma models

    International Nuclear Information System (INIS)

    Gates, S.J. Jr.

    1983-07-01

    The superspace formulation of two classes of supersymmetric nonlinear σ-models are presented. Two alternative N=1 superspace formulations are given for the d=2 supersymmetric nonlinear σ-models with Killing vector potentials: (a) formulation uses an active central charge and, (b) formulation uses a spurion superfield without inducing a classical breakdown of supersymmetry. The N=2 vector multiplet is used to construct a new class of d=4 nonlinear σ-models which when reduced to d=2 possess N=4 supersymmetry. Implications of these two classes of nonlinear σ-models for N>=4 superfield supergravity are discussed. (author)

  15. 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.

  16. 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.

  17. 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.

  18. Novel formulations and new mechanisms of delivering chemotherapy.

    Science.gov (United States)

    Stinchcombe, Thomas E

    2014-01-01

    The identification of epidermal growth factor receptor mutations and anaplastic lymphoma kinase rearrangements and the development of targeted therapy for patients with these molecular alterations has been a tremendous advance in the treatment of advanced stage or metastatic non-small cell lung cancer (NSCLC). However, the majority of patients with advanced stage NSCLC will not have one of these molecular alterations and will receive chemotherapy as their primary therapy. Chemotherapy remains a critical component of therapy for resected and locally advanced NSCLC, as well as for patients with limited-stage and extensive stage small cell lung cancer (SCLC). A significant unmet need exists to develop novel chemotherapy agents and to improve the efficacy and toxicity of currently available agents. Several novel formulations of currently available chemotherapy agents are in development for NSCLC and SCLC. Antibody conjugates are therapeutic agents that employ a tumor-specific monoclonal antibody conjugated to a cytotoxic or radionuclide agent. After the monoclonal antibody binds to the tumor antigen, these agents are internalized, and the link between the antibody and the therapeutic agent is dissolved and the cytotoxic agent is release intracellularly. This enhanced delivery of chemotherapy to malignant tissues has the potential to improve efficacy and reduce toxicity. Antibody conjugates to therapeutic agents are currently available for other malignancies and are in development for NSCLC and SCLC.

  19. Optimization of carboxylate-terminated poly(amidoamine) dendrimer-mediated cisplatin formulation.

    Science.gov (United States)

    Kulhari, Hitesh; Pooja, Deep; Singh, Mayank K; Chauhan, Abhay S

    2015-02-01

    Abstract Cisplatin is mainly used in the treatment of ovarian, head and neck and testicular cancer. Poor solubility and non-specific interactions causes hurdles in the development of successful cisplatin formulation. There were few reports on poly(amidoamine) (PAMAM) dendrimer-cisplatin complexes for anticancer treatment. But the earlier research was mainly focused on therapeutic effect of PAMAM dendrimer-cisplatin complex, with less attention paid on the formulation development of these complexes. Objective of the present study is to optimize and validate the carboxylate-terminated, EDA core PAMAM dendrimer-based cisplatin formulation with respect to various variables such as dendrimer core, generation, drug entrapment, purification, yield, reproducibility, stability, storage and in-vitro release. Dendrimer-cisplatin complex was prepared by an efficient method which significantly increases the % platinum (Pt) content along with the product yield. Dendrimers showed reproducible (∼27%) platinum loading by weight. Variation in core and generations does not produce significant change in the % Pt content. Percentage Pt content of dendrimeric formulation increases with increase in drug/dendrimer mole ratio. Formulation with low drug/dendrimer mole ratio showed delayed release compared to the higher drug/dendrimer mole ratio; these dendrimer formulations are stable in room temperature. In vitro release profiles of the stored dendrimer-cisplatin samples showed comparatively slow release of cisplatin, which may be due to formation of strong bond between cisplatin and dendrimer. This study will contribute to create a fine print for the formulation development of PAMAM dendrimer-cisplatin complexes.

  20. Glass Ceramic Formulation Data Package

    International Nuclear Information System (INIS)

    Crum, Jarrod V.; Rodriguez, Carmen P.; McCloy, John S.; Vienna, John D.; Chung, Chul-Woo

    2012-01-01

    A glass ceramic waste form is being developed for treatment of secondary waste streams generated by aqueous reprocessing of commercial used nuclear fuel (Crum et al. 2012b). The waste stream contains a mixture of transition metals, alkali, alkaline earths, and lanthanides, several of which exceed the solubility limits of a single phase borosilicate glass (Crum et al. 2009; Caurant et al. 2007). A multi-phase glass ceramic waste form allows incorporation of insoluble components of the waste by designed crystallization into durable heat tolerant phases. The glass ceramic formulation and processing targets the formation of the following three stable crystalline phases: (1) powellite (XMoO4) where X can be (Ca, Sr, Ba, and/or Ln), (2) oxyapatite Yx,Z(10-x)Si6O26 where Y is alkaline earth, Z is Ln, and (3) lanthanide borosilicate (Ln5BSi2O13). These three phases incorporate the waste components that are above the solubility limit of a single-phase borosilicate glass. The glass ceramic is designed to be a single phase melt, just like a borosilicate glass, and then crystallize upon slow cooling to form the targeted phases. The slow cooling schedule is based on the centerline cooling profile of a 2 foot diameter canister such as the Hanford High-Level Waste canister. Up to this point, crucible testing has been used for glass ceramic development, with cold crucible induction melter (CCIM) targeted as the ultimate processing technology for the waste form. Idaho National Laboratory (INL) will conduct a scaled CCIM test in FY2012 with a glass ceramic to demonstrate the processing behavior. This Data Package documents the laboratory studies of the glass ceramic composition to support the CCIM test. Pacific Northwest National Laboratory (PNNL) measured melt viscosity, electrical conductivity, and crystallization behavior upon cooling to identify a processing window (temperature range) for melter operation and cooling profiles necessary to crystallize the targeted phases in the

  1. Graphene-based platforms for cancer therapeutics

    Science.gov (United States)

    Patel, Sunny C; Lee, Stephen; Lalwani, Gaurav; Suhrland, Cassandra; Chowdhury, Sayan Mullick; Sitharaman, Balaji

    2016-01-01

    Graphene is a multifunctional carbon nanomaterial and could be utilized to develop platform technologies for cancer therapies. Its surface can be covalently and noncovalently functionalized with anticancer drugs and functional groups that target cancer cells and tissue to improve treatment efficacies. Furthermore, its physicochemical properties can be harnessed to facilitate stimulus responsive therapeutics and drug delivery. This review article summarizes the recent literature specifically focused on development of graphene technologies to treat cancer. We will focus on advances at the interface of graphene based drug/gene delivery, photothermal/photodynamic therapy and combinations of these techniques. We also discuss the current understanding in cytocompatibility and biocompatibility issues related to graphene formulations and their implications pertinent to clinical cancer management. PMID:26769305

  2. NOSH-aspirin (NBS-1120), a novel nitric oxide- and hydrogen sulfide-releasing hybrid has enhanced chemo-preventive properties compared to aspirin, is gastrointestinal safe with all the classic therapeutic indications

    Science.gov (United States)

    Kodela, Ravinder; Chattopadhyay, Mitali; Velázquez-Martínez, Carlos A.; Kashfi, Khosrow

    2015-01-01

    Aspirin is chemopreventive; however, side effects preclude its long-term use. NOSH-aspirin (NBS-1120), a novel hybrid that releases nitric oxide and hydrogen sulfide, was designed to be a safer alternative. Here we compare the gastrointestinal safety, anti-inflammatory, analgesic, antipyretic, anti-platelet, and chemopreventive properties of aspirin and NBS-1120 administered orally to rats at equimolar doses. Gastrointestinal safety: 6h post-administration, the number and size of hemorrhagic lesions in stomachs were counted; tissue samples were frozen for PGE2, SOD, and MDA determination. Anti-inflammatory: 1h after drug administration, the volume of carrageenan-induced rat paw edemas was measured for 5h. Anti-pyretic: fever was induced by LPS (ip) an hour before administration of the test drugs, core body temperature was measured hourly for 5h. Analgesic: time-dependent analgesic effects were evaluated by carrageenan-induced hyperalgesia. Antiplatelet: anti-aggregatory effects were studied on collagen-induced platelet aggregation of human platelet-rich plasma. Chemoprevention: Nude mice were gavaged daily for 25 days with vehicle, aspirin or NBS-1120. After one week, each mouse was inoculated subcutaneously in the right flank with HT-29 human colon cancer cells. Both agents reduced PGE2 levels in stomach tissue; however, NBS-1120 did not cause any stomach ulcers, whereas aspirin caused significant bleeding. Lipid peroxidation induced by aspirin was higher than that exerted by NBS-1120. SOD activity was significantly inhibited by aspirin but increased by NBS-1120. Both agents showed similar anti-inflammatory, analgesic, anti-pyretic, and anti-platelet activities. Aspirin increased plasma TNFα more than NBS-1120-treated animals. NBS-1120 was better than aspirin as a chemopreventive agent; it dose-dependently inhibited tumor growth and tumor mass. PMID:26394025

  3. Therapeutic effects of L-Cysteine in newborn mice subjected to hypoxia-ischemia brain injury via the CBS/H2S system: Role of oxidative stress and endoplasmic reticulum stress.

    Science.gov (United States)

    Liu, Song; Xin, Danqing; Wang, Lingxiao; Zhang, Tiantian; Bai, Xuemei; Li, Tong; Xie, Yunkai; Xue, Hao; Bo, Shishi; Liu, Dexiang; Wang, Zhen

    2017-10-01

    Neonatal hypoxic-ischemic (HI) injury is a major cause of neonatal death and neurological dysfunction. H 2 S has been shown to protect against hypoxia-induced injury and apoptosis of neurons. L-Cysteine is catalyzed by cystathionine-β-synthase (CBS) in the brain and sequentially produces endogenous H 2 S. The present study was designed to investigate whether L-Cysteine could attenuate the acute brain injury and improve neurobehavioral outcomes following HI brain injury in neonatal mice by releasing endogenous H 2 S. L-Cysteine treatment significantly attenuated brain edema and decreased infarct volume and neuronal cell death, as shown by a decrease in the Bax/Bcl-2 ratio, suppression of caspase-3 activation, and reduced phosphorylation of Akt and ERK at 72h after HI. Additionally, L-Cysteine substantially up-regulated NF-E2-related factor 2 and heme oxygenase-1 expression. L-Cysteine also decreased endoplasmic reticulum (ER) stress-associated pro-apoptotic protein expression. Furthermore, L-Cysteine had long-term effects by protecting against the loss of ipsilateral brain tissue and improving neurobehavioral outcomes. Importantly, pre-treatment with a CBS inhibitor significantly attenuated the neuroprotection of L-Cysteine on HI insult. Thus, L-Cysteine exerts neuroprotection against HI-induced injury in neonates via the CBS/H 2 S pathway, mediated in part by anti-apoptotic effects and reduced oxidative stress and ER stress. Thus, L-Cysteine may be a promising treatment for HI. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  4. Polyaniline: Aniline oxidation with strong and weak oxidants under various acidity

    Energy Technology Data Exchange (ETDEWEB)

    Bláha, Michal, E-mail: blaha@imc.cas.cz [Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, 162 06 Prague 6 (Czech Republic); Trchová, Miroslava; Bober, Patrycja; Morávková, Zuzana [Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, 162 06 Prague 6 (Czech Republic); Prokeš, Jan [Charles University, Faculty of Mathematics and Physics, 180 00 Prague 8 (Czech Republic); Stejskal, Jaroslav [Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, 162 06 Prague 6 (Czech Republic)

    2017-06-15

    Aniline was oxidized with three strong inorganic oxidants (ammonium peroxydisulfate, cerium(IV) sulfate, potassium dichromate), two weak inorganic oxidants (iron(III) chloride, silver nitrate), and one organic oxidant (p-benzoquinone) in aqueous solutions of methanesulfonic acid (MSA) of various concentration. Whereas oxidation of aniline with ammonium peroxydisulfate yielded high-molecular-weight conducting polyaniline (PANI) in the whole acidity range, the oxidation with cerium(IV) sulfate led also to a single product close to PANI with considerably lower molecular weight and lower conductivity. Potassium dichromate gave PANI only at high concentration of MSA. The use of iron(III) chloride yielded composite mixtures of PANI and low-molecular-weight aniline oligomers. The oxidation of aniline with silver nitrate led to composites of silver and an organic part, which was constituted either by aniline oligomers or conducting polyaniline or both. p-Benzoquinone as oxidant produced mainly aniline oligomers with poor conductivity and 2,5-dianilino-p-benzoquinone-like structure detected in FTIR and Raman spectra when oxidation proceeded with weak oxidants. A general model of oxidation with strong and weak oxidants was formulated. - Highlights: • Comparison of aniline oxidation with oxidants of different redox potential. • UV–vis, FTIR and Raman spectroscopies combined with size-exclusion chromatography. • The contents of polymer and oligomers were analyzed and discussed. • General model of aniline oxidation with strong and weak oxidants was formulated.

  5. Antibody Engineering and Therapeutics

    Science.gov (United States)

    Almagro, Juan Carlos; Gilliland, Gary L; Breden, Felix; Scott, Jamie K; Sok, Devin; Pauthner, Matthias; Reichert, Janice M; Helguera, Gustavo; Andrabi, Raiees; Mabry, Robert; Bléry, Mathieu; Voss, James E; Laurén, Juha; Abuqayyas, Lubna; Barghorn, Stefan; Ben-Jacob, Eshel; Crowe, James E; Huston, James S; Johnston, Stephen Albert; Krauland, Eric; Lund-Johansen, Fridtjof; Marasco, Wayne A; Parren, Paul WHI; Xu, Kai Y

    2014-01-01

    The 24th Antibody Engineering & Therapeutics meeting brought together a broad range of participants who were updated on the latest advances in antibody research and development. Organized by IBC Life Sciences, the gathering is the annual meeting of The Antibody Society, which serves as the scientific sponsor. Preconference workshops on 3D modeling and delineation of clonal lineages were featured, and the conference included sessions on a wide variety of topics relevant to researchers, including systems biology; antibody deep sequencing and repertoires; the effects of antibody gene variation and usage on antibody response; directed evolution; knowledge-based design; antibodies in a complex environment; polyreactive antibodies and polyspecificity; the interface between antibody therapy and cellular immunity in cancer; antibodies in cardiometabolic medicine; antibody pharmacokinetics, distribution and off-target toxicity; optimizing antibody formats for immunotherapy; polyclonals, oligoclonals and bispecifics; antibody discovery platforms; and antibody-drug conjugates. PMID:24589717

  6. [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.

  7. A comparison of Fick and Maxwell-Stefan diffusion formulations in PEMFC gas diffusion layers

    Science.gov (United States)

    Lindstrom, Michael; Wetton, Brian

    2017-01-01

    This paper explores the mathematical formulations of Fick and Maxwell-Stefan diffusion in the context of polymer electrolyte membrane fuel cell cathode gas diffusion layers. The simple Fick law with a diagonal diffusion matrix is an approximation of Maxwell-Stefan. Formulations of diffusion combined with mass-averaged Darcy flow are considered for three component gases. For this application, the formulations can be compared computationally in a simple, one dimensional setting. Despite the models' seemingly different structure, it is observed that the predictions of the formulations are very similar on the cathode when air is used as oxidant. The two formulations give quite different results when the Nitrogen in the air oxidant is replaced by helium (this is often done as a diagnostic for fuel cells designs). The two formulations also give quite different results for the anode with a dilute Hydrogen stream. These results give direction to when Maxwell-Stefan diffusion, which is more complicated to implement computationally in many codes, should be used in fuel cell simulations.

  8. A New Resistance Formulation for Carbon Nanotubes

    Directory of Open Access Journals (Sweden)

    Ji-Huan He

    2008-01-01

    Full Text Available A new resistance formulation for carbon nanotubes is suggested using fractal approach. The new formulation is also valid for other nonmetal conductors including nerve fibers, conductive polymers, and molecular wires. Our theoretical prediction agrees well with experimental observation.

  9. Advanced Query Formulation in Deductive Databases.

    Science.gov (United States)

    Niemi, Timo; Jarvelin, Kalervo

    1992-01-01

    Discusses deductive databases and database management systems (DBMS) and introduces a framework for advanced query formulation for end users. Recursive processing is described, a sample extensional database is presented, query types are explained, and criteria for advanced query formulation from the end user's viewpoint are examined. (31…

  10. Aerosol formulation and clinical efficacy of bronchodilators

    NARCIS (Netherlands)

    Zanen, Pieter

    1998-01-01

    This thesis subject is the improvement of the formulation of inhaled aerosols. It is well known that the formulation of inhaled drugs is not optimal: the major part of the mass delivered does not reach the lower airways. This phenomenon is due to the particle size of the inhaled particles, which

  11. Hamiltonian formulation of anomaly free chiral bosons

    International Nuclear Information System (INIS)

    Abdalla, E.; Abdalla, M.C.B.; Devecchi, F.P.; Zadra, A.

    1988-01-01

    Starting out of an anomaly free Lagrangian formulation for chiral scalars, which a Wess-Zumino Term (to cancel the anomaly), we formulate the corresponding hamiltonian problem. Ther we use the (quantum) Siegel invariance to choose a particular, which turns out coincide with the obtained by Floreanini and Jackiw. (author) [pt

  12. Undefined cellulase formulations hinder scientific reproducibility.

    Science.gov (United States)

    Himmel, Michael E; Abbas, Charles A; Baker, John O; Bayer, Edward A; Bomble, Yannick J; Brunecky, Roman; Chen, Xiaowen; Felby, Claus; Jeoh, Tina; Kumar, Rajeev; McCleary, Barry V; Pletschke, Brett I; Tucker, Melvin P; Wyman, Charles E; Decker, Stephen R

    2017-01-01

    In the shadow of a burgeoning biomass-to-fuels industry, biological conversion of lignocellulose to fermentable sugars in a cost-effective manner is key to the success of second-generation and advanced biofuel production. For the effective comparison of one cellulase preparation to another, cellulase assays are typically carried out with one or more engineered cellulase formulations or natural exoproteomes of known performance serving as positive controls. When these formulations have unknown composition, as is the case with several widely used commercial products, it becomes impossible to compare or reproduce work done today to work done in the future, where, for example, such preparations may not be available. Therefore, being a critical tenet of science publishing, experimental reproducibility is endangered by the continued use of these undisclosed products. We propose the introduction of standard procedures and materials to produce specific and reproducible cellulase formulations. These formulations are to serve as yardsticks to measure improvements and performance of new cellulase formulations.

  13. Formulation of gastroretentive floating drug delivery system using hydrophilic polymers and its in vitro characterization

    Directory of Open Access Journals (Sweden)

    Venkata Srikanth Meka

    2014-04-01

    Full Text Available The aim of the present research is to formulate and evaluate the gastroretentive floating drug delivery system of antihypertensive drug, propranolol HCl. Gastroretentive floating tablets (GRFT were prepared by using a synthetic hydrophilic polymer polyethylene oxide of different grades such as PEO WSR N-12 K and PEO 18 NF as release retarding polymers and calcium carbonate as gas generating agent. The GRFT were compressed by direct compression strategy and the tablets were evaluated for physico-chemical properties, in vitro buoyancy, swelling studies, in vitro dissolution studies and release mechanism studies. From the dissolution and buoyancy studies, F 9 was selected as an optimized formulation. The optimized formulation followed zero order rate kinetics with non-Fickian diffusion mechanism. The optimized formulation was characterised with FTIR studies and observed no interaction between the drug and the polymers.

  14. Neuroprotective and neurorescue effects of a novel polymeric nanoparticle formulation of curcumin (NanoCurc™) in the neuronal cell culture and animal model: implications for Alzheimer's disease.

    Science.gov (United States)

    Ray, Balmiki; Bisht, Savita; Maitra, Amarnath; Maitra, Anirban; Lahiri, Debomoy K

    2011-01-01

    Alzheimer's disease (AD) is characterized by deposition of amyloid-β (Aβ) plaques within the brain parenchyma followed by synaptic loss and neuronal death. Deposited Aβ reacts with activated microglia to produce reactive oxygen species (ROS) and cytochemokines, which lead to severe neuroinflammation. Curcumin is a yellow polyphenol compound found in turmeric, a widely used culinary ingredient that possesses anti-inflammatory and anti-cancer properties and may show efficacy as a potential therapeutic agent in several neuro-inflammatory diseases including AD. However, poor aqueous solubility and sub-optimal systemic absorption from the gastrointestinal tract may represent factors contributing to its failure in clinical trials. To increase curcumin's bioavailability, a polymeric nanoparticle encapsulated curcumin (NanoCurc™) was formulated which is completely water soluble. NanoCurc™ treatment protects neuronally differentiated human SK-N-SH cells from ROS (H2O2) mediated insults. NanoCurc™ also rescues differentiated human SK-N-SH cells, which were previously insulted with H2O2. In vivo, intraperitoneal (IP) NanoCurc™ injection at a dose of 25mg/kg twice daily in athymic mice resulted in significant curcumin levels in the brain (0.32 μg/g). Biochemical study of NanoCurc™-treated athymic mice revealed decreased levels of H2O2 as well as caspase 3 and caspase 7 activities in the brain, accompanied by increased glutathione (GSH) concentrations. Increased free to oxidized glutathione (GSH:GSSH) ratio in athymic mice brain versus controls also indicated a favorable redox intracellular environment. Taken together, these results suggest that NanoCurc™ represents an optimized formulation worthy of assessing the therapeutic value of curcumin in AD.

  15. Comparative Plasma Exposure and Lung Distribution of Two Human Use Commercial Azithromycin Formulations Assessed in Murine Model: A Preclinical Study

    OpenAIRE

    Rivulgo, Virginia Margarita; Sparo, Mónica; Ceci, Mónica; Fumuso, Elida; Confalonieri, Alejandra; Delpech, Gastón; Sanchez Bruni, Sergio Fabian

    2016-01-01

    Azithromycin(AZM)therapeutic failure and relapses of patients treated with generic -35 formulations have been observed in clinical practice.The main goal of this research was 36 to compare in a pre-clinical study the serum exposure and lung tissue concentrationof 37 two commercial formulations AZM-based in murine model. The current study involved 38 264 healthy Balb-C.Mice were divided in two groups (n=44): Animals of Group A 39 (Reference Formulation ?R-) were orally treated with AZM suspens...

  16. Formulation of heat absorbing glasses

    Directory of Open Access Journals (Sweden)

    Álvarez-Casariego, Pedro

    1996-06-01

    Full Text Available In the thermal exchanges between buildings and environment, glazing is an element of major importance, for it largely influences the so-called Solar Heat Gain and Thermal Losses. These parameters can be modified by applying different type of coatings onto glass surface or by adding colorant compounds during glass melting. The latter is a cheaper way to control the Solar Heat Gain. The knowledge of the laws governing the interaction between colorant compounds and solar radiation, allows us to define glass formulations achieving specific aesthetic requirements and solar energy absorption. In this paper two examples of application of the modelling of glass colorants spectral absorptance are presented. First is addressed to obtaining a glass with high luminous transmittance and low solar energy transmittance, and the other one to obtaining a glass with neutral colour appearance and minimized solar energy transmittance. Calculation formulas are defined together with photometric properties so-obtained. These type of glasses are particularly suitable to be used as building and automotive glazing, for they retain the mechanical characteristics and possibilities of transformation of standard glass.

    En los intercambios de energía entre un edificio y el medio exterior, el vidrio es el elemento de mayor importancia, por su influencia en la Ganancia de Calor Solar y en las Pérdidas Térmicas. Estos parámetros pueden ser modificados mediante el depósito de capas sobre el vidrio o mediante la adición de compuestos absorbentes de la radiación solar. Esta última vía es la más económica para controlar la Ganancia de Calor Solar. El conocimiento de las leyes que gobiernan la interacción de los diversos colorantes con la radiación solar, permite definir formulaciones de vidrios con características especificas de tipo estético y de absorción energética. En este trabajo se presentan dos ejemplos de aplicación de esta modelización de las

  17. [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.

  18. Tablet coating by injection molding technology - Optimization of coating formulation attributes and coating process parameters.

    Science.gov (United States)

    Desai, Parind M; Puri, Vibha; Brancazio, David; Halkude, Bhakti S; Hartman, Jeremy E; Wahane, Aniket V; Martinez, Alexander R; Jensen, Keith D; Harinath, Eranda; Braatz, Richard D; Chun, Jung-Hoon; Trout, Bernhardt L

    2018-01-01

    We developed and evaluated a solvent-free injection molding (IM) coating technology that could be suitable for continuous manufacturing via incorporation with IM tableting. Coating formulations (coating polymers and plasticizers) were prepared using hot-melt extrusion and screened via stress-strain analysis employing a universal testing machine. Selected coating formulations were studied for their melt flow characteristics. Tablets were coated using a vertical injection molding unit. Process parameters like softening temperature, injection pressure, and cooling temperature played a very important role in IM coating processing. IM coating employing polyethylene oxide (PEO) based formulations required sufficient room humidity (>30% RH) to avoid immediate cracks, whereas other formulations were insensitive to the room humidity. Tested formulations based on Eudrajit E PO and Kollicoat IR had unsuitable mechanical properties. Three coating formulations based on hydroxypropyl pea starch, PEO 1,000,000 and Opadry had favorable mechanical (35% elongation, >95×10 4 J/m 3 toughness) and melt flow (>0.4g/min) characteristics, that rendered acceptable IM coats. These three formulations increased the dissolution time by 10, 15 and 35min, respectively (75% drug release), compared to the uncoated tablets (15min). Coated tablets stored in several environmental conditions remained stable to cracking for the evaluated 8-week time period. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Triphala, Ayurvedic formulation for treating and preventing cancer: a review.

    Science.gov (United States)

    Baliga, Manjeshwar Shrinath

    2010-12-01

    Triphala (Sanskrit tri = three and phala = fruits), composed of the three medicinal fruits Phyllanthus emblica L. or Emblica officinalis Gaertn., Terminalia chebula Retz., and Terminalia belerica Retz. is an important herbal preparation in the traditional Indian system of medicine, Ayurveda. Triphala is an antioxidant-rich herbal formulation and possesses diverse beneficial properties. It is a widely prescribed Ayurvedic drug and is used as a colon cleanser, digestive, diuretic, and laxative. Cancer is a major cause of death, and globally studies are being conducted to prevent cancer or to develop effective nontoxic therapeutic agents. Experimental studies in the past decade have shown that Triphala is useful in the prevention of cancer and that it also possesses antineoplastic, radioprotective and chemoprotective effects. This review for the first time summarizes these results, with emphasis on published observations. Furthermore, the possible mechanisms responsible for the beneficial effects and lacunas in the existing knowledge that need to be bridged are also discussed.

  20. Molecularly targeted therapeutic radiopharmaceuticals

    International Nuclear Information System (INIS)

    Saw, M.M.

    2007-01-01

    Full text: It is generally agreed that current focus of nuclear medicine development should be on molecular imaging and therapy. Though, the widespread use of the terminology 'molecular imaging' is quite recent, nuclear medicine has used molecular imaging techniques for more than 20 years ago. A variety of radiopharmaceuticals have been introduced for the internal therapy of malignant and inflammatory lesions in nuclear medicine. In the field of bio/medical imaging, nuclear medicine is one of the disciplines which has the privilege of organized and well developed chemistry/ pharmacy section; radio-chemistry/radiopharmacy. Fundamental principles have been developed more than 40 years ago and advanced research is going well into postgenomic era. The genomic revolution and dramatically increased insight in the molecular mechanisms underlying pathology have led to paradigm shift in drug development. Likewise does in the nuclear medicine. Here, the author will present current clinical and pre-clinical therapeutic radiopharmaceuticals based on molecular targets such as membrane-bound receptors, enzymes, nucleic acids, sodium iodide symporter, etc, in correlation with fundamentals of radiopharmacy. (author)

  1. 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...... underpinnings for the need to separate research and treatment, and thus the notion of therapeutic misconception in the fi rst place. We call this tension between research and treatment ambivalent research advancement to highlight the difficulties that various actors have in managing such shifts within...

  2. 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

  3. Therapeutic cloning in the mouse

    Science.gov (United States)

    Mombaerts, Peter

    2003-01-01

    Nuclear transfer technology can be applied to produce autologous differentiated cells for therapeutic purposes, a concept termed therapeutic cloning. Countless articles have been published on the ethics and politics of human therapeutic cloning, reflecting the high expectations from this new opportunity for rejuvenation of the aging or diseased body. Yet the research literature on therapeutic cloning, strictly speaking, is comprised of only four articles, all in the mouse. The efficiency of derivation of embryonic stem cell lines via nuclear transfer is remarkably consistent among these reports. However, the efficiency is so low that, in its present form, the concept is unlikely to become widespread in clinical practice. PMID:12949262

  4. Canonical operator formulation of nonequilibrium thermodynamics

    International Nuclear Information System (INIS)

    Mehrafarin, M.

    1992-09-01

    A novel formulation of nonequilibrium thermodynamics is proposed which emphasises the fundamental role played by the Boltzmann constant k in fluctuations. The equivalence of this and the stochastic formulation is demonstrated. The k → 0 limit of this theory yields the classical deterministic description of nonequilibrium thermodynamics. The new formulation possesses unique features which bear two important results namely the thermodynamic uncertainty principle and the quantisation of entropy production rate. Such a theory becomes indispensable whenever fluctuations play a significant role. (author). 7 refs

  5. Application of UV Imaging in Formulation Development

    DEFF Research Database (Denmark)

    Sun, Yu; Østergaard, Jesper

    2017-01-01

    defining formulation behavior after exposure to the aqueous environments and pharmaceutical performance is critical in pharmaceutical development, manufacturing and quality control of drugs. UV imaging has been explored as a tool for qualitative and quantitative characterization of drug dissolution...... related to the structural properties of the drug substance or formulation can be monitored. UV imaging is a non-intrusive and simple-to-operate analytical technique which holds potential for providing a mechanistic foundation for formulation development. This review aims to cover applications of UV...

  6. Formulation of 11-dimensional supergravity in superspace

    International Nuclear Information System (INIS)

    Cremmer, E.; Ferrara, S.

    1980-01-01

    We formulate on-shell 11-dimensional supergravity in superspace and express its equations of motion in terms of purely geometrical quantities. All torsion and curvature components are solved in terms of a single superfield Wsub(rstu), totally antisymmetric in its (flat vector) indices. The dimensional reduction of this formulation is expected to be related to the superspace formulation of N = 8 extended supergravity and might explain the origin of the hidden (local) SU(8) and (global) E 7 symmetries present in this theory. (orig.)

  7. An exact approach for aggregated formulations

    DEFF Research Database (Denmark)

    Gamst, Mette; Spoorendonk, Simon; Røpke, Stefan

    Aggregating formulations is a powerful approach for problems to take on tractable forms. Aggregation may lead to loss of information, i.e. the aggregated formulation may be an approximation of the original problem. In branch-and-bound context, aggregation can also complicate branching, e.g. when...... optimality cannot be guaranteed by branching on aggregated variables. We present a generic exact solution method to remedy the drawbacks of aggregation. It combines the original and aggregated formulations and applies Benders' decomposition. We apply the method to the Split Delivery Vehicle Routing Problem....

  8. CRYSTALLINE CERAMIC WASTE FORMS: REFERENCE FORMULATION REPORT

    Energy Technology Data Exchange (ETDEWEB)

    Brinkman, K.; Fox, K.; Marra, J.

    2012-05-15

    The research conducted in this work package is aimed at taking advantage of the long term thermodynamic stability of crystalline ceramics to create more durable waste forms (as compared to high level waste glass) in order to reduce the reliance on engineered and natural barrier systems. Durable ceramic waste forms that incorporate a wide range of radionuclides have the potential to broaden the available disposal options and to lower the storage and disposal costs associated with advanced fuel cycles. Assemblages of several titanate phases have been successfully demonstrated to incorporate radioactive waste elements, and the multiphase nature of these materials allows them to accommodate variation in the waste composition. Recent work has shown that they can be successfully produced from a melting and crystallization process. The objective of this report is to explain the design of ceramic host systems culminating in a reference ceramic formulation for use in subsequent studies on process optimization and melt property data assessment in support of FY13 melter demonstration testing. The waste stream used as the basis for the development and testing is a combination of the projected Cs/Sr separated stream, the Trivalent Actinide - Lanthanide Separation by Phosphorous reagent Extraction from Aqueous Komplexes (TALSPEAK) waste stream consisting of lanthanide fission products, the transition metal fission product waste stream resulting from the transuranic extraction (TRUEX) process, and a high molybdenum concentration with relatively low noble metal concentrations. In addition to the combined CS/LN/TM High Mo waste stream, variants without Mo and without Mo and Zr were also evaluated. Based on the results of fabricating and characterizing several simulated ceramic waste forms, two reference ceramic waste form compositions are recommended in this report. The first composition targets the CS/LN/TM combined waste stream with and without Mo. The second composition targets

  9. Shared written case formulations and weight change in outpatient therapy for anorexia nervosa: a naturalistic single case series.

    Science.gov (United States)

    Gladwin, Alice M; Evangeli, Michael

    2013-01-01

    The therapeutic effects of written shared case formulations are underexplored and have not been examined in anorexia nervosa. This study explored the relationship between (a) the delivery (b) the quality of a shared written case formulation and weight in outpatient psychological therapy for anorexia nervosa. A naturalistic single case series approach was used to examine the case notes of women who had attended a specialist eating disorders service over a 2-year period. The case notes of 15 adult women who had undergone outpatient psychological therapy for anorexia nervosa with a shared written case formulation component were reviewed. The impact of the quality of the case formulation on weekly weight was examined for 14 of the clients where the case formulation was available. The nature of the relationship between the delivery of the written shared case formulation and weight was examined for all 15 clients. There was some evidence to support an association between delivery of the shared written case formulation and weight changes (both weight gain [five out of 15 clients] and weight loss [three out of 15 clients]) in individual cases. Higher case formulation quality was related to cases where weight change did not occur. The delivery of case formulations can be associated with important therapeutic change (both beneficial and potentially harmful) in anorexia nervosa. Future research into the causal mechanisms associated with sharing formulations will face the challenge of adopting strategies that allow for an in-depth exploration of complex therapy variables whilst overcoming methodological challenges. Copyright © 2012 John Wiley & Sons, Ltd.

  10. New tablet formulation of tacrolimus with smaller interindividual variability may become a better treatment option than the conventional capsule formulation in organ transplant patients

    Directory of Open Access Journals (Sweden)

    Kim YK

    2017-09-01

    Full Text Available Yu Kyong Kim,1 Anhye Kim,1,2 Shin Jung Park,3 Howard Lee1,4 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, 2Clinical Trial Center, Ajou University Medical Center, Suwon, 3Research Institute, Chong Kun Dang Pharmaceutical Corp, Yongin, 4Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Suwon, Republic of Korea Abstract: To evaluate the pharmacokinetic (PK and tolerability profiles of a new tablet formulation of tacrolimus and its interindividual variability (IIV in the systemic exposure, and to compare them with those of the conventional capsule formulation, a randomized, open-label, two-treatment, two-period, two-sequence, crossover study was performed in 47 healthy males. The capsule or tablet formulation of tacrolimus was orally administered, and serial blood samples were collected up to 96 hours after dosing. Whole-blood tacrolimus concentration was determined using liquid chromatography–tandem mass spectrometry. The maximum whole-blood tacrolimus concentration (Cmax and the area under the whole-blood tacrolimus concentration–time curve from 0 hour to the last quantifiable concentration (AUClast were compared between the two formulations. The similarity factor (f2 of the in vitro dissolution profiles was calculated. The geometric mean ratio (90% confidence interval of tablet to capsule was 0.9680 (0.8873–1.0560 and 1.0322 (0.9359–1.1385 for Cmax and AUClast, respectively. The IIV of Cmax and AUClast of the tablet was smaller than the capsule. The f2 values were >50 in all media. Both formulations were well tolerated. Thus, the tablet formulation of tacrolimus has smaller IIV in the systemic exposure than capsule, while having comparable PK and tolerability profiles, which may render it as a better treatment option for organ transplant patients. Keywords: new formulation, incrementally

  11. Pharmacokinetics of Short- and Long-acting Formulations of Oxytetracycline After Intramuscular Administration in Chickens.

    Science.gov (United States)

    Gberindyer, Aondover F; Okpeh, Ene R; Semaka, Asaaga A

    2015-12-01

    Both short- and long-acting formulations of oxytetracycline are commonly used in veterinary medicine to treat animals infected with gram-negative and gram-positive bacteria, rickettsiae, mycoplasma, and chlamydiae. To compare pharmacokinetics of short- and long-acting oxytetracycline in chickens, injectable formulations from the same pharmaceutical company were administered to healthy 6-week-old broiler chickens in accordance to the labeled instructions. Fourteen chickens were separated into 2 groups: chickens in group A (n = 7) were administered the short-acting formulation (10 mg/kg IM q24h) for 4 consecutive days, whereas those in group B (n = 7) were treated with a single dose (20 mg/kg IM) of the long-acting formulation. Blood samples were collected into heparinized tubes before and at 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 10, and 24 hours after initial treatment. Thereafter, blood samples were taken every 24 hours up to 120 hours. Plasma concentrations of oxytetracycline were determined by competitive enzyme-linked immunoabsorbent assay, and pharmacokinetic parameters were obtained. Both formulations delivered therapeutic plasma concentrations of oxytetracycline for approximately 100% of their respective dosing intervals as recommended. However, considering the additional labor, patient stress, and mortalities associated with handling, in addition to rejection of the carcass due to tissue necrosis resulting from multiple injections, we recommend use of the long-acting instead of the short-acting injectable formulation in broiler chickens.

  12. Inhibiting mitochondrial β-oxidation selectively reduces levels of nonenzymatic oxidative polyunsaturated fatty acid metabolites in the brain.

    Science.gov (United States)

    Chen, Chuck T; Trépanier, Marc-Olivier; Hopperton, Kathryn E; Domenichiello, Anthony F; Masoodi, Mojgan; Bazinet, Richard P

    2014-03-01

    Schönfeld and Reiser recently hypothesized that fatty acid β-oxidation is a source of oxidative stress in the brain. To test this hypothesis, we inhibited brain mitochondrial β-oxidation with methyl palmoxirate (MEP) and measured oxidative polyunsaturated fatty acid (PUFA) metabolites in the rat brain. Upon MEP treatment, levels of several nonenzymatic auto-oxidative PUFA metabolites were reduced with few effects on enzymatically derived metabolites. Our finding confirms the hypothesis that reduced fatty acid β-oxidation decreases oxidative stress in the brain and β-oxidation inhibitors may be a novel therapeutic approach for brain disorders associated with oxidative stress.

  13. Paradoxical Roles of Nanoparticles in Cancer Therapeutics and Carcinogenesis

    Science.gov (United States)

    Despeaux, Emily

    Nanoparticles (NPs) are becoming increasingly common in consumer goods and are under investigation for a variety of industrial and biomedical applications. However, challenges in determining NP toxicity may prevent them from reaching their full potential. NPs cannot be treated as single class for toxicity evaluations. Even among particles made from the same material, particle-specific physical properties, including size, shape, surface charge, agglomeration state, and surface modifications have a strong effect on the toxicity. Even so, the obstacles to conclusively and reproducibly evaluating toxicity span all NP classes. NP literature is riddled with confusing and often contradictory reports regarding the biocompatibility of both engineered NPs, designed with biocompatibility as a priority, and NPs from occupational or environmental exposures. Incomplete NP characterization and sample inhomogeneity represent major confounding factors in disparate results from seemingly comparable study setups. Additionally, NPs can interfere with many conventional toxicity screening methods. Inappropriate doses, exposure routes, and toxicity endpoints further diminish the utility of many published studies. Given the burgeoning interest in NP-based therapeutic agents, consistent, reliable standards are needed to ensure the biocompatibility of new formulations. To those ends, the synthesis, characterization, and in vitro toxicity of a multi-functional NP therapeutic were investigated (Chapter 2). Specifically, superparamagnetic iron oxide nanoparticles (SPIONs) were coated with amphiphilic polymer and functionalized with antisense oligonucleotides targeting survivin, an anti-apoptotic protein that is highly overexpressed in cancer. SPION physical properties, including particle size and composition, were characterized at each step of synthesis. Our results showed that the SPION platform is biocompatible and capable of delivering functional antisense oligonucleotides to regulate

  14. Synthesis and formulation of 99m Tc-ECD radiopharmaceutical

    International Nuclear Information System (INIS)

    Ocampo G, B.E.

    1998-01-01

    Nuclear medicine is a medical specialty which uses radioactive compounds (radionuclides) for diagnostic and therapeutic purposes. 99m Tc is the more common radionuclide used in many studies in nuclear medicine because its advantages: it has a photopeak of 140 KeV and a half-life of 6 hours; it can be eluted from a Molybdenum 99 generator, so radiopharmaceuticals can be prepared on site. Ethyl cysteine dimer (ECD) labelled with reduced Technetium 99m has been purposed recently as a promising radiopharmaceutical for brain perfusion imaging 99m Tc-ECD is a lipophilic neutral complex which cross the brain blood barrier and show high brain uptake. The objective of this work was synthesize and to design a freeze dried formulation for the instant preparation of 99m Tc-ECD complex useful for brain perfusion imaging. We obtained a freeze dried stable formulation for the preparation of 99m Tc-ECD kit with a radiochemical purity higher than 90 %, which fulfills with the quality control of radiopharmaceuticals. Furthermore, we developed analytic techniques for the determination of the different chemical compounds into the lyophilized kit. (Author)

  15. Nanoparticle Formulation Derived from Carboxymethyl Cellulose, Polyethylene Glycol, and Cabazitaxel for Chemotherapy Delivery to the Brain.

    Science.gov (United States)

    Bteich, Joseph; Ernsting, Mark J; Mohammed, Mohammed; Kiyota, Taira; McKee, Trevor D; Trikha, Mohit; Lowman, Henry B; Sokoll, Kenneth K

    2018-05-23

    Nanoparticles provide a unique opportunity to explore the benefits of selective distribution and release of cancer therapeutics at sites of disease through varying particle sizes and compositions that exploit the enhanced permeability of tumor-associated blood vessels. Though delivery of larger as opposed to smaller and/or actively transported molecules to the brain is prima facie a challenging endeavor, we wondered whether nanoparticles could improve the therapeutic index of existing drugs for use in treating brain tumors via these vascular effects. We therefore selected a family of nanoparticles composed of cabazitaxel-carboxymethyl cellulose amphiphilic polymers to investigate the potential for delivering a brain-penetrant taxane to intracranial brain tumors in mice. Among a small set of nanoparticle formulations, we found evidence for nanoparticle accumulation in the brain, and one such formulation demonstrated activity in an orthotopic model of glioma, suggesting that such nanoparticles could be useful for the treatment of glioma and brain metastases of other tumor types.

  16. Safety and efficacy of generic drugs with respect to brand formulation.

    Science.gov (United States)

    Gallelli, Luca; Palleria, Caterina; De Vuono, Antonio; Mumoli, Laura; Vasapollo, Piero; Piro, Brunella; Russo, Emilio

    2013-12-01

    Generic drugs are equivalent to the brand formulation if they have the same active substance, the same pharmaceutical form and the same therapeutic indications and a similar bioequivalence respect to the reference medicinal product. The use of generic drugs is indicated from many countries in order to reduce medication price. However some points, such as bioequivalence and the role of excipients, may be clarified regarding the clinical efficacy and safety during the switch from brand to generic formulations. In conclusion, the use of generic drugs could be related with an increased days of disease (time to relapse) or might lead to a therapeutic failure; on the other hand, a higher drug concentration might expose patients to an increased risk of dose-dependent side-effects.

  17. 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.

  18. Dental therapeutic systems.

    Science.gov (United States)

    Iqbal, Zeenat; Jain, Nilu; Jain, Gaurav K; Talegaonkar, Sushama; Ahuja, Alka; Khar, Roop K; Ahmad, Farhan J

    2008-01-01

    The recognition of periodontal diseases as amenable to local antibiotherapy has resulted in a paradigmatic shift in treatment modalities of dental afflictions. Moreover the presence of antimicrobial resistance, surfacing of untoward reactions owing to systemic consumption of antibiotics has further advocated the use of local delivery of physiologically active substances into the periodontal pocket. While antimicrobials polymerized into acrylic strips, incorporated into biodegradable collagen and hollow permeable cellulose acetate fibers, multiparticulate systems, bio-absorbable dental materials, biodegradable gels/ointments, injectables, mucoadhesive microcapsules and nanospheres will be more amenable for direct placement into the periodontal pockets the lozenges, buccoadhesive tablets, discs or gels could be effectively used to mitigate the overall gingival inflammation. Whilst effecting controlled local delivery of a few milligram of an antibacterial agent within the gingival crevicular fluid for a longer period of time, maintaining therapeutic concentrations such delivery devices will circumvent all adverse effects to non- oral sites. Since the pioneering efforts of Goodson and Lindhe in 1989, delivery at gingival and subgingival sites has witnessed a considerable progress. The interest in locally active systems is evident from the patents being filed and granted. The present article shall dwell in reviewing the recent approaches being proffered in the field. Patents as by Shefer, et al. US patent, 6589562 dealing with multicomponent biodegradable bioadhesive controlled release system for oral care products, Lee, et al. 2001, US patent 6193994, encompassing a locally administrable, biodegradable and sustained-release pharmaceutical composition for periodontitis and process for preparation thereof and method of treating periodontal disease as suggested by Basara in 2004via US patent 6830757, shall be the types of intellectual property reviewed and presented in

  19. 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

  20. Curcumin: Reintroduced Therapeutic Agent from Traditional Medicine for Alcoholic Liver Disease

    Directory of Open Access Journals (Sweden)

    Hamid Reza Rahimi

    2015-03-01

    Full Text Available Alcoholic liver disease (ALD is the main cause of chronic liver disease across the world and can lead to fibrosis and cirrhosis. The etiopathogenesis of ALD is related to ethanol-induced oxidative stress, glutathione reduction, abnormal methionine metabolism, malnutrition, and production of endotoxins that activate Kupffer cells. Curcumin is an active ingredient of the rhizome of turmeric. The substance is shown to have minor adverse effects. As the substance possess low bioavailability in free formulation, different strategies has been conducted to improve its bioavailability which resulted in production of nanomiscels and nanoparticles. Curcumin can provide protection for the liver against toxic effects of alcohol use. Several studies showed curcumin blocks endotoxin-mediated activation of NF-κB and suppresses the expression of cytokines, chemokines, COX-2, and iNOS in Kupffer cells. According to the molecular studies, curcumin inhibits NF-κB signaling pathway, regulates cytokines production and modulates immune response. It has been shown that curcumin can suppress gene expression, especially cytokines genes resulting in down-regulation of tumor necrosis factor-α (TNF-α, interleukin 1 (IL-1, IL-6, IL-8, adhesion molecules (ICAM, VCAM and C-reactive protein. Hence, curcumin can have therapeutic effects on the majority of chronic inflammatory diseases such as asthma, bronchitis, inflammatory bowel disease, rheumatoid arthritis, ALD, fatty liver, and allergy.

  1. Chemical-Based Formulation Design: Virtual Experimentation

    DEFF Research Database (Denmark)

    Conte, Elisa; Gani, Rafiqul

    This paper presents a software, the virtual Product-Process Design laboratory (virtual PPD-lab) and the virtual experimental scenarios for design/verification of consumer oriented liquid formulated products where the software can be used. For example, the software can be employed for the design......, the additives and/or their mixtures (formulations). Therefore, the experimental resources can focus on a few candidate product formulations to find the best product. The virtual PPD-lab allows various options for experimentations related to design and/or verification of the product. For example, the selection...... design, model adaptation). All of the above helps to perform virtual experiments by blending chemicals together and observing their predicted behaviour. The paper will highlight the application of the virtual PPD-lab in the design and/or verification of different consumer products (paint formulation...

  2. Understanding Pesticide Risks: Toxicity and Formulation

    OpenAIRE

    Muntz, Helen; Miller, Rhonda; Alston, Diane

    2016-01-01

    This fact sheet provides information about pesticide risks to human health, primary means of pesticide exposure, standardized measures of pesticide toxicity, pesticide signal words and type of pesticide formulations.

  3. Emulsifying Formulation of Rosuvastatin Calcium for Improved ...

    African Journals Online (AJOL)

    solubility study, liquid formulations were prepared using LAS/Capryol 90: Maisine 35-1 as oil phase and. Tween 20 with ... evaluated for globule size, zeta potential, and emulsion properties. ..... surfactants which decreases the electrostatic.

  4. Dynamic psychiatry and the psychodynamic formulation

    African Journals Online (AJOL)

    processes and psychiatric disorders are biological, the range ... The formulation furthermore helps with the initial orientation towards the patient: it anticipates and predicts how the patient ..... contributed to problems with his sexual identity.

  5. Formulation of Thermosensitive Hydrogel Containing Cyclodextrin ...

    African Journals Online (AJOL)

    Materials. Chitosan (deacetylation degree, DDA = 80 %) was obtained from HiMedia Laboratories Pvt. ... Sterile formulations were ... Chilled β-GP aqueous solution (sterilized through ..... generally decreasing away from the center of the tumor.

  6. Current advances on polynomial resultant formulations

    Science.gov (United States)

    Sulaiman, Surajo; Aris, Nor'aini; Ahmad, Shamsatun Nahar

    2017-08-01

    Availability of computer algebra systems (CAS) lead to the resurrection of the resultant method for eliminating one or more variables from the polynomials system. The resultant matrix method has advantages over the Groebner basis and Ritt-Wu method due to their high complexity and storage requirement. This paper focuses on the current resultant matrix formulations and investigates their ability or otherwise towards producing optimal resultant matrices. A determinantal formula that gives exact resultant or a formulation that can minimize the presence of extraneous factors in the resultant formulation is often sought for when certain conditions that it exists can be determined. We present some applications of elimination theory via resultant formulations and examples are given to explain each of the presented settings.

  7. Formulation and Characterization of Biodegradable Medicated ...

    African Journals Online (AJOL)

    PEG)-600, tributyl citrate, PEG-200, PEG-300, PEG-400, PEG-4000, triethyl citrate and castor oil. The gum formulations were characterized for the following parameters: texture profile analysis (TPA), biodegradation, in vitro drug release using a ...

  8. A simplectic formulation of relativistic particle dynamics

    International Nuclear Information System (INIS)

    Tulczyjew, W.M.

    1976-12-01

    Particle mechanics is formulated in terms of symplectic relations and infinitesimal symplectic relations. Generating functions of symplectic relations are shown to be classical counterparts of Green's functions of wave mechanics. (orig.) [de

  9. A sympletic formulation of relativistic particle dynamics

    International Nuclear Information System (INIS)

    Tulczyjew, W.M.

    1977-01-01

    Particle mechanics is formulated in terms of sympletic relations and infinitesimal symplectic relations. Generating functions of symplectic relations are shown to be classical counterparts of Green's functions of wave mechanics. (author)

  10. Paclitaxel Albumin-stabilized Nanoparticle Formulation

    Science.gov (United States)

    This page contains brief information about paclitaxel albumin-stabilized nanoparticle formulation and a collection of links to more information about the use of this drug, research results, and ongoing clinical trials.

  11. The Boltzmann equation in the difference formulation

    Energy Technology Data Exchange (ETDEWEB)

    Szoke, Abraham [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Brooks III, Eugene D. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2015-05-06

    First we recall the assumptions that are needed for the validity of the Boltzmann equation and for the validity of the compressible Euler equations. We then present the difference formulation of these equations and make a connection with the time-honored Chapman - Enskog expansion. We discuss the hydrodynamic limit and calculate the thermal conductivity of a monatomic gas, using a simplified approximation for the collision term. Our formulation is more consistent and simpler than the traditional derivation.

  12. Limitations of high dose carrier based formulations.

    Science.gov (United States)

    Yeung, Stewart; Traini, Daniela; Tweedie, Alan; Lewis, David; Church, Tanya; Young, Paul M

    2018-06-10

    This study was performed to investigate how increasing the active pharmaceutical ingredient (API) content within a formulation affects the dispersion of particles and the aerosol performance efficiency of a carrier based dry powder inhalable (DPI) formulation, using a custom dry powder inhaler (DPI) development rig. Five formulations with varying concentrations of API beclomethasone dipropionate (BDP) between 1% and 30% (w/w) were formulated as a multi-component carrier system containing coarse lactose and fine lactose with magnesium stearate. The morphology of the formulation and each component were investigated using scanning electron micrographs while the particle size was measured by laser diffraction. The aerosol performance, in terms of aerodynamic diameter, was assessed using the British pharmacopeia Apparatus E cascade impactor (Next generation impactor). Chemical analysis of the API was observed by high performance liquid chromatography (HPLC). Increasing the concentration of BDP in the blend resulted in increasing numbers and size of individual agglomerates and densely packed BDP multi-layers on the surface of the lactose carrier. BDP present within the multi-layer did not disperse as individual primary particles but as dense agglomerates, which led to a decrease in aerosol performance and increased percentage of BDP deposition within the Apparatus E induction port and pre-separator. As the BDP concentration in the blends increases, aerosol performance of the formulation decreases, in an inversely proportional manner. Concurrently, the percentage of API deposition in the induction port and pre-separator could also be linked to the amount of micronized particles (BDP and Micronized composite carrier) present in the formulation. The effect of such dose increase on the behaviour of aerosol dispersion was investigated to gain greater insight in the development and optimisation of higher dosed carrier-based formulations. Copyright © 2018 Elsevier B.V. All

  13. Chemicals-Based Formulation Design: Virtual Experimentations

    DEFF Research Database (Denmark)

    Conte, Elisa; Gani, Rafiqul

    2011-01-01

    This paper presents a systematic procedure for virtual experimentations related to the design of liquid formulated products. All the experiments that need to be performed when designing a liquid formulated product (lotion), such as ingredients selection and testing, solubility tests, property mea...... on the design of an insect repellent lotion will show that the software is an essential instrument in decision making, and that it reduces time and resources since experimental efforts can be focused on one or few product alternatives....

  14. Comments on alternate formulations for preequilibrium decay

    International Nuclear Information System (INIS)

    Blann, M.

    1978-01-01

    The physical and mathematical differences of several formulations for preequilibrium decay are discussed. Mathematical models and examples are presented or referred to in order to illustrate what the author believes to be errors in the exciton formulation as being due to improper inclusion of spectator effects. An earlier work of Gadioli et al. is reinterpreted, and quotations therein to work of the present author are corrected

  15. The redox biology network in cancer pathophysiology and therapeutics

    Directory of Open Access Journals (Sweden)

    Gina Manda

    2015-08-01

    Full Text Available The review pinpoints operational concepts related to the redox biology network applied to the pathophysiology and therapeutics of solid tumors. A sophisticated network of intrinsic and extrinsic cues, integrated in the tumor niche, drives tumorigenesis and tumor progression. Critical mutations and distorted redox signaling pathways orchestrate pathologic events inside cancer cells, resulting in resistance to stress and death signals, aberrant proliferation and efficient repair mechanisms. Additionally, the complex inter-cellular crosstalk within the tumor niche, mediated by cytokines, redox-sensitive danger signals (HMGB1 and exosomes, under the pressure of multiple stresses (oxidative, inflammatory, metabolic, greatly contributes to the malignant phenotype. The tumor-associated inflammatory stress and its suppressive action on the anti-tumor immune response are highlighted. We further emphasize that ROS may act either as supporter or enemy of cancer cells, depending on the context. Oxidative stress-based therapies, such as radiotherapy and photodynamic therapy, take advantage of the cytotoxic face of ROS for killing tumor cells by a non-physiologically sudden, localized and intense oxidative burst. The type of tumor cell death elicited by these therapies is discussed. Therapy outcome depends on the differential sensitivity to oxidative stress of particular tumor cells, such as cancer stem cells, and therefore co-therapies that transiently down-regulate their intrinsic antioxidant system hold great promise. We draw attention on the consequences of the damage signals delivered by oxidative stress-injured cells to neighboring and distant cells, and emphasize the benefits of therapeutically triggered immunologic cell death in metastatic cancer. An integrative approach should be applied when designing therapeutic strategies in cancer, taking into consideration the mutational, metabolic, inflammatory and oxidative status of tumor cells, cellular

  16. Understanding and modulating opalescence and viscosity in a monoclonal antibody formulation

    OpenAIRE

    Salinas, Branden A; Sathish, Hasige A; Bishop, Steven M; Harn, Nick; Carpenter, John F; Randolph, Theodore W

    2010-01-01

    Opalescence and high viscosities can pose challenges for high concentration formulation of antibodies. Both phenomena result from protein-protein intermolecular interactions that can be modulated with solution ionic strength. We studied a therapeutic monoclonal antibody that exhibits high viscosity in solutions at low ionic strength (~20 centipoise (cP) at 90 mg/mL and 23°C) and significant opalescence at isotonic ionic strength (approximately 100 nephelometric turbidity units at 90 mg/mL and...

  17. Safety and efficacy of generic drugs with respect to brand formulation

    OpenAIRE

    Gallelli, Luca; Palleria, Caterina; De Vuono, Antonio; Mumoli, Laura; Vasapollo, Piero; Piro, Brunella; Russo, Emilio

    2013-01-01

    Generic drugs are equivalent to the brand formulation if they have the same active substance, the same pharmaceutical form and the same therapeutic indications and a similar bioequivalence respect to the reference medicinal product. The use of generic drugs is indicated from many countries in order to reduce medication price. However some points, such as bioequivalence and the role of excipients, may be clarified regarding the clinical efficacy and safety during the switch from brand to gener...

  18. The coevent formulation of quantum theory

    International Nuclear Information System (INIS)

    Wallden, Petros

    2013-01-01

    Understanding quantum theory has been a subject of debate from its birth. Many different formulations and interpretations have been proposed. Here we examine a recent novel formulation, namely the coevents formulation. It is a histories formulation and has as starting point the Feynman path integral and the decoherence functional. The new ontology turns out to be that of a coarse-grained history. We start with a quantum measure defined on the space of histories, and the existence of zero covers rules out single-history as potential reality (the Kochen Specker theorem casted in histories form is a special case of a zero cover). We see that allowing coarse-grained histories as potential realities avoids the previous paradoxes, maintains deductive non-contextual logic (alas non-Boolean) and gives rise to a unique classical domain. Moreover, we can recover the probabilistic predictions of quantum theory with the use of the Cournot's principle. This formulation, being both a realist formulation and based on histories, is well suited conceptually for the purposes of quantum gravity and cosmology.

  19. An herbal formulation for hemorrhoids treatment

    Directory of Open Access Journals (Sweden)

    S. Dehdari

    2017-11-01

    Full Text Available Background and objectives: Hemorrhoids is the most painful rectal disease. Straining and pregnancy seem playing chief roles in the development of hemorrhoids. Symptoms of hemorrhoids may include bleeding, inflammation and pain. Despite current medical efforts, many discomforts of hemorrhoids have not been handled. The aim of the present study was to formulate and evaluate Itrifal-e muqil (IM tablet to achieve desired pharmaceutical properties. Method: Quality control tests of Allium ampeloperasum L, Commiphora mukul (Hook. ex Stocks Engl., Phyllanthus emblica L., Terminalia chebula Retz. and Terminalia bellerica Retz. were performed. Afterwards, different formulations were prepared and their physical properties were evaluated. Subsequently, the formulation was coated and its physicochemical characteristics were assessed. Result: All of the herbs demonstrated good results in quality control tests according to United State Pharmacopeia (USP. Formulation-1 that was completely prepared based on explained manufacturing process of IM in traditional medicine manuscripts did not show suitable pharmaceutical properties. Among different formulations, Formulation-3 that consisted of A. ampeloperasum, C. mukul, P. emblica, T. chebula and T. bellerica, displayed best outcomes through different tests. Conclusion: Modern pharmaceutical approaches can excellently be adapted for IM preparations.

  20. Sub-therapeutic doses of fluvastatin and valsartan are more effective than therapeutic doses in providing beneficial cardiovascular pleiotropic effects in rats: A proof of concept study.

    Science.gov (United States)

    Janić, Miodrag; Lunder, Mojca; France Štiglic, Alenka; Jerin, Aleš; Skitek, Milan; Černe, Darko; Marc, Janja; Drevenšek, Gorazd; Šabovič, Mišo

    2017-12-01

    Statins and sartans can, in therapeutic doses, induce pleiotropic cardiovascular effects. Similar has recently been shown also for sub-therapeutic doses. We thus explored and compared the cardiovascular pleiotropic efficacy of sub-therapeutic vs. therapeutic doses. Wistar rats were randomly divided into 7 groups receiving fluvastatin, valsartan and their combination in sub-therapeutic and therapeutic doses, or saline. After 6weeks, the animals were euthanised, their hearts and thoracic aortas isolated, and blood samples taken. Endothelium-dependent relaxation of the thoracic aortae and ischaemic-reperfusion injury of the isolated hearts were assessed along with the related serum parameters and genes expression. Fluvastatin and valsartan alone or in combination were significantly more effective in sub-therapeutic than therapeutic doses. The sub-therapeutic combination greatly increased thoracic aorta endothelium-dependent relaxation and maximally protected the isolated hearts against ischaemia-reperfusion injury and was thus most effective. Beneficial effects were accompanied by increased levels of nitric oxide (NO) and decreased levels of asymmetric dimethylarginine (ADMA) in the serum (again prominently induced by the sub-therapeutic combination). Furthermore, nitric oxide synthase 3 (NOS3) and endothelin receptor type A (EDNRA) genes expression increased, but only in both combination groups and without significant differences between them. In the therapeutic dose groups, fluvastatin and valsartan decreased cholesterol values and systolic blood pressure. Sub-therapeutic doses of fluvastatin and valsartan are more effective in expressing cardiovascular pleiotropic effects than therapeutic doses of fluvastatin and/or valsartan. These results could be of significant clinical relevance. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Therapeutic Inertia and Treatment Intensification.

    Science.gov (United States)

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

    2018-01-29

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

  2. Current issues of RNAi therapeutics delivery and development.

    Science.gov (United States)

    Haussecker, D

    2014-12-10

    the applications of RNAi therapeutics are rather limited. This is largely based on the observation that the biodistribution of RNAi formulations is typically more limited compared to small molecules and oral administration is not possible with current technologies. Similarly, the utility of a given RNAi formulation is limited to a few cell types and tissues at most and a universal delivery strategy should remain elusive for the foreseeable future. Therefore, to further expand on the therapeutic utility and patient convenience of RNAi, it is important to overcome a number of delivery-related technical and scientific challenges which will be discussed in this presentation. For systemic applications, these include the necessity for extended blood circulation times, vascular escape (probably the most rewarding inquiry currently), tissue penetration, cellular uptake, and escape into the cytoplasm. In terms of safety, it is important that these formulations do not accumulate in the body, do not cause excessive off-targeting due to 'chemical stickiness' (often useful for purposes of biodistribution), and overcome the physical/biological barriers in a controlled manner. The time for realizing the therapeutic potential of RNAi has come. At the same time, it is important to lay the foundations for the next leg of value creation by overcoming the challenges of delivering RNAi to new cell types. Based on results from exploratory research, the renewed interest in RNAi therapeutics and capital infusion, there is a reason to be optimistic that this can be achieved. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Formulation of Dipyridamole Sustained Release Tablet Using Floating System

    Directory of Open Access Journals (Sweden)

    Lenny Mauilida Valentina

    2011-06-01

    Full Text Available Dipyridamole is a drug for prevention of postoperative thromboembolic complication of heart valve replacement and long term therapy of angina pectoris will be well absorbed in stomach. To maintain therapeutic plasma concentration in long time and to increase bioavalaibility is needed a sustained release dosage form having the long residence time in the stomach. The objective of this research was to make floating sustained release tablet of dipyridamole conforming to the requirement that was set up by dipyridamol therapeutic concentration. Tablets were made by wet granulation method using aquadest as a liquid binder, HPMC K4M, Ac-di-sol, Avicel PH 102, talk, and Mg stearat. Dissolution assay was carried out using type 2 release tester at rotation speed of 50 rpm in medium 900 mL HCl 0.1 N at 37 ± 0.5 °C for 8 hours. The formulation containing of 50 mg dipirydamole, HPMC K4M (30%, Ac-di-sol (20%, Avicel PH 102 (37%, talk (2%, and Mg stearat (1% released 59.61 ± 6.73% and 89.34 ± 5.87% of dipyridamole respectively after 4 and 8 hours that conformed to the requirement.

  4. Challenges in the development of magnetic particles for therapeutic applications.

    Science.gov (United States)

    Barry, Stephen E

    2008-09-01

    Certain iron-based particle formulations have useful magnetic properties that, when combined with low toxicity and desirable pharmacokinetics, encourage their development for therapeutic applications. This mini-review begins with background information on magnetic particle use as MRI contrast agents and the influence of material size on pharmacokinetics and tissue penetration. Therapeutic investigations, including (1) the loading of bioactive materials, (2) the use of stationary, high-gradient (HG) magnetic fields to concentrate magnetic particles in tissues or to separate material bound to the particles from the body, and (3) the application of high power alternating magnetic fields (AMF) to generate heat in magnetic particles for hyperthermic therapeutic applications are then surveyed. Attention is directed mainly to cancer treatment, as selective distribution to tumors is well-suited to particulate approaches and has been a focus of most development efforts. While magnetic particles have been explored for several decades, their use in therapeutic products remains minimal; a discussion of future directions and potential ways to better leverage magnetic properties and to integrate their use into therapeutic regimens is discussed.

  5. Sustained release of intravitreal flurbiprofen from a novel drug-in-liposome-in-hydrogel formulation.

    Science.gov (United States)

    Pachis, K; Blazaki, S; Tzatzarakis, M; Klepetsanis, P; Naoumidi, E; Tsilimbaris, M; Antimisiaris, S G

    2017-11-15

    A novel Flurbiprofen (FLB)-in-liposome-in-hydrogel formulation was developed, as a method to sustain the release and increase the ocular bioavailability of FLB following intravitreal injection. For this, FLB loading into liposomes was optimized and liposomes were entrapped in thermosensitive hydrogels consisted of Pluronic F-127 (P). FLB solution, liposomes, and FLB dissolved in hydrogel were also used as control formulations. Actively loaded liposomes were found to be optimal for high FLB loading and small size, while in vitro studies revealed that P concentration of 18% (w/v) was best to retain the integrity of the hydrogel-dispersed liposome, compared to a 20% concentration. The in vitro release of FLB was significantly sustained when FLB-liposomes were dispersed in the hydrogel compared to hydrogel dissolved FLB, as well as the other control formulations. In vivo studies were carried out in pigmented rabbits which were injected through a 27G needle with 1mg/mL FLB in the different formulation-types. Ophthalmic examinations after intravitreal injection of all FLB formulations, revealed no evidence of inflammation, hemorrhage, uveitis or endophthalmitis. Pharmacokinetic analysis results confirm that the hybrid drug delivery system increases the bioavailability (by 1.9 times compared to solution), and extends the presence of the drug in the vitreous cavity, while liposome and hydrogel formulations demonstrate intermediate performance. Furthermore the hybrid system increases MRT of FLB in aqueous humor and retina/choroid tissues, compared to all the control formulations. Currently the potential therapeutic advances of FLB sustained release formulations for IVT administration are being evaluated. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Platelet lysate formulations based on mucoadhesive polymers for the treatment of corneal lesions.

    Science.gov (United States)

    Sandri, Giuseppina; Bonferoni, Maria Cristina; Rossi, Silvia; Ferrari, Franca; Mori, Michela; Del Fante, Claudia; Perotti, Cesare; Scudeller, Luigia; Caramella, Carla

    2011-02-01

    Growth factors contained in platelet α-granules initiate and modulate tissue repair and are proposed for the treatment of soft and hard-tissue surgical conditions and in the management of non-healing wounds. Platelet lysate is a hemoderivative obtained from platelet-rich plasma and is capable of releasing a pool of growth factors. Many medical and surgical techniques have been proposed for the treatment of corneal lesions; management of these conditions remains problematic and healing with standard protocols is unattainable. The aim of this study was to develop formulations suitable for prolonging the contact of platelet lysate with the damaged cornea for the time necessary to exert a therapeutic effect. Two vehicles, one based on polyacrylic acid and one based on chitosan, were autoclaved and loaded with platelet lysate and the resultant formulations were characterized for rheology, mucoadhesion, vehicle compatibility and stability. The proliferation effect was tested on two cell culture types (rabbit corneal epithelial cells and fibroblasts). An in-vitro wound-healing test was performed on fibroblasts. In both cases the formulations were compared with platelet lysate diluted with saline at the same concentration. Both formulations maintained the rheological and mucoadhesive properties of the vehicles and the proliferative activity of platelet lysate. The chitosan formulation was able to significantly enhance epithelial cell growth even after storage of up to 2 weeks (in-use conditions), while the polyacrylic acid formulation was less efficient, probably due to the characteristics of the cell model used. The in-vitro wound-healing test performed on fibroblasts confirmed the differences between the two vehicles. The effect induced by the platelet lysate and chitosan formulation was faster than that of the polyacrylic acid formulation and complete in-vitro wound repair was achieved within 48 h. © 2010 The Authors. JPP © 2010 Royal Pharmaceutical Society.

  7. Formulation studies for mirtazapine orally disintegrating tablets.

    Science.gov (United States)

    Yıldız, Simay; Aytekin, Eren; Yavuz, Burçin; Bozdağ Pehlivan, Sibel; Ünlü, Nurşen

    2016-01-01

    Orally disintegrating tablets (ODTs) recently have gained much attention to fulfill the needs for pediatric, geriatric, and psychiatric patients with dysphagia. Aim of this study was to develop new ODT formulations containing mirtazapine, an antidepressant drug molecule having bitter taste, by using simple and inexpensive preparation methods such as coacervation, direct compression and to compare their characteristics with those of reference product (Remereon SolTab). Coacervation method was chosen for taste masking of mirtazapine. In vitro characterization studies such as diameter and thickness, weight variation, tablet hardness, tablet friability and disintegration time were performed on tablet formulations. Wetting time and in vitro dissolution tests of developed ODTs also studied using 900 mL 0.1 N HCl medium, 900 mL pH 6.8 phosphate buffer or 900 mL pH 4.5 acetate buffer at 37 ± 0.2 °C as dissolution medium. Ratio of Eudragit® E-100 was chosen as 6% (w/w) since the dissolution profile of A1 (6% Eudragit® E-100) was found closer to the reference product than A2 (4% Eudragit® E-100) and A3 (8% Eudragit® E-100). Group D, E and F formulations were presented better results in terms of disintegration time. Dissolution results indicated that Group E and F formulations showed optimum properties in all three dissolution media. Formulations D1, D4, D5, E3, E4, F1 and F5 found suitable as ODT formulations due to their favorable disintegration times and dissolution profiles. Developed mirtazapine ODTs were found promising in terms of showing the similar characteristics to the original formulation.

  8. TURVA-2012: Formulation of radionuclide release scenarios

    International Nuclear Information System (INIS)

    Marcos, Nuria; Hjerpe, Thomas; Snellman, Margit; Ikonen, Ari; Smith, Paul

    2014-01-01

    TURVA-2012 is Posiva's safety case in support of the Preliminary Safety Analysis Report (PSAR) and application for a construction licence for a repository for disposal of spent nuclear fuel at the Olkiluoto site in south-western Finland. This paper gives a summary of the scenarios and the methodology followed in formulating them as described in TURVA-2012: Formulation of Radionuclide Release Scenarios (Posiva, 2013). The scenarios are further analysed in TURVA-2012: Assessment of Radionuclide Release Scenarios for the Repository System and TURVA-2012: Biosphere Assessment (Posiva, 2012a, 2012b). The formulation of scenarios takes into account the safety functions of the main barriers of the repository system and the uncertainties in the features, events, and processes (FEP) that may affect the entire disposal system (i.e. repository system plus the surface environment) from the emplacement of the first canister until the far future. In the report TURVA-2012: Performance Assessment (2012d), the performance of the engineered and natural barriers has been assessed against the loads expected during the evolution of the repository system and the site. Uncertainties have been identified and these are taken into account in the formulation of radionuclide release scenarios. The uncertainties in the FEP and evolution of the surface environment are taken into account in formulating the surface environment scenarios used ultimately in estimating radiation exposure. Formulating radionuclide release scenarios for the repository system links the reports Performance Assessment and Assessment of Radionuclide Release Scenarios for the Repository System. The formulation of radionuclide release scenarios for the surface environment brings together biosphere description and the surface environment FEP and is the link to the assessment of the surface environment scenarios summarised in TURVA-2012: Biosphere Assessment. (authors)

  9. Natural products against Alzheimer's disease: Pharmaco-therapeutics and biotechnological interventions.

    Science.gov (United States)

    Dey, Abhijit; Bhattacharya, Raktim; Mukherjee, Anuradha; Pandey, Devendra Kumar

    Alzheimer's disease (AD) is a severe, chronic and progressive neurodegenerative disease associated with memory and cognition impairment ultimately leading to death. It is the commonest reason of dementia in elderly populations mostly affecting beyond the age of 65. The pathogenesis is indicated by accumulation of the amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFT) in brain tissues and hyperphosphorylation of tau protein in neurons. The main cause is considered to be the formation of reactive oxygen species (ROS) due to oxidative stress. The current treatment provides only symptomatic relief by offering temporary palliative therapy which declines the rate of cognitive impairment associated with AD. Inhibition of the enzyme acetylcholinesterase (AChE) is considered as one of the major therapeutic strategies offering only symptomatic relief and moderate disease-modifying effect. Other non-cholinergic therapeutic approaches include antioxidant and vitamin therapy, stem cell therapy, hormonal therapy, use of antihypertensive or lipid-lowering medications and selective phosphodiesterase (PDE) inhibitors, inhibition of β-secretase and γ-secretase and Aβ aggregation, inhibition of tau hyperphosphorylation and intracellular NFT, use of nonsteroidal anti-inflammatory drugs (NSAIDs), transition metal chelators, insulin resistance drugs, etanercept, brain-derived neurotrophic factor (BDNF) etc. Medicinal plants have been reported for possible anti-AD activity in a number of preclinical and clinical trials. Ethnobotany, being popular in China and in the Far East and possibly less emphasized in Europe, plays a substantial role in the discovery of anti-AD agents from botanicals. Chinese Material Medica (CMM) involving Chinese medicinal plants has been used traditionally in China in the treatment of AD. Ayurveda has already provided numerous lead compounds in drug discovery and many of these are also undergoing clinical investigations. A number of medicinal plants

  10. Human Factor in Therapeutic Relationship

    Directory of Open Access Journals (Sweden)

    Ramazan Akdogan

    2011-03-01

    Full Text Available herapeutic relationship is a professional relationship that has been structured based on theoretical props. This relationship is a complicated, wide and unique relationship which develops between two people, where both sides' personality and attitudes inevitably interfere. Therapist-client relationship experienced through transference and counter transference, especially in psychodynamic approaches, is accepted as the main aspect of therapeutic process. However, the approaches without dynamic/deterministic tendency also take therapist-client relationship into account seriously and stress uniqueness of interaction between two people. Being a person and a human naturally sometimes may negatively influence the relationship between the therapist and client and result in a relationship going out of the theoretical frame at times. As effective components of a therapeutic process, the factors that stem from being human include the unique personalities of the therapist and the client, their values and their attitude either made consciously or subconsciously. Literature has shown that the human-related factors are too effective to be denied in therapeutic relationship process. Ethical and theoretical knowledge can be inefficient to prevent the negative effects of these factors in therapeutic process at which point a deep insight and supervision would have a critical role in continuing an acceptable therapeutic relationship. This review is focused on the reflection of some therapeutic factors resulting from being human and development of counter transference onto the therapeutic process.

  11. Lipid Based Formulations of Biopharmaceutics Classification System (BCS Class II Drugs: Strategy, Formulations, Methods and Saturation

    Directory of Open Access Journals (Sweden)

    Šoltýsová I.

    2016-12-01

    Full Text Available Active ingredients in pharmaceuticals differ by their physico-chemical properties and their bioavailability therefore varies. The most frequently used and most convenient way of administration of medicines is oral, however many drugs are little soluble in water. Thus they are not sufficiently effective and suitable for such administration. For this reason a system of lipid based formulations (LBF was developed. Series of formulations were prepared and tested in water and biorelevant media. On the basis of selection criteria, there were selected formulations with the best emulsification potential, good dispersion in the environment and physical stability. Samples of structurally different drugs included in the Class II of the Biopharmaceutics classification system (BCS were obtained, namely Griseofulvin, Glibenclamide, Carbamazepine, Haloperidol, Itraconazol, Triclosan, Praziquantel and Rifaximin, for testing of maximal saturation in formulations prepared from commercially available excipients. Methods were developed for preparation of formulations, observation of emulsification and its description, determination of maximum solubility of drug samples in the respective formulation and subsequent analysis. Saturation of formulations with drugs showed that formulations 80 % XA and 20 % Xh, 35 % XF and 65 % Xh were best able to dissolve the drugs which supports the hypothesis that it is desirable to identify limited series of formulations which could be generally applied for this purpose.

  12. Role of oxidative stress in therapeutic administration of artesunate ...

    African Journals Online (AJOL)

    The effects of antioxidants, vitamins C and E, on sperm quality, testosterone levels, superoxide dismutase (SOD) activity and malondialdehyde (MDA) concentration were studied in artesunate treated rats. 25 male rats (160 to 250 g) divided into five groups were used for the study. Group 1 animals received normal saline ...

  13. Formulation of Sustained-Release Diltiazem Matrix Tablets Using ...

    African Journals Online (AJOL)

    Erah

    surface, their drug release behavior appears simple, but ... matrix material for the formulation of ..... formulation F5 (,) and reference formulations. ( , □). 0. 50. 100. 150. 200. 250. 300. 0. 3. 6 .... Coviello T, Matricardi P, Marianecci C, Alhaique F.

  14. Hydroxypropyl-β-cyclodextrin–graphene oxide conjugates: Carriers for anti-cancer drugs

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Jingting; Meng, Na; Fan, Yunting; Su, Yutian; Zhang, Ming [Jiangsu Collaborative Innovation Center for Biological Functional Materials, College of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023 (China); National and Local Joint Engineering Research Center of Biomedical Functional Materials, Nanjing 210023 (China); Jiangsu Key Laboratory of Biofunctional Materials, Jiangsu Engineering Research Center for Biomedical Function Materials, Nanjing 210023 (China); Xiao, Yinghong, E-mail: yhxiao@njnu.edu.cn [Jiangsu Collaborative Innovation Center for Biological Functional Materials, College of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023 (China); National and Local Joint Engineering Research Center of Biomedical Functional Materials, Nanjing 210023 (China); Jiangsu Key Laboratory of Biofunctional Materials, Jiangsu Engineering Research Center for Biomedical Function Materials, Nanjing 210023 (China); Zhou, Ninglin, E-mail: zhouninglin@njnu.edu.cn [Jiangsu Collaborative Innovation Center for Biological Functional Materials, College of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023 (China); National and Local Joint Engineering Research Center of Biomedical Functional Materials, Nanjing 210023 (China); Jiangsu Key Laboratory of Biofunctional Materials, Jiangsu Engineering Research Center for Biomedical Function Materials, Nanjing 210023 (China); Nanjing Zhou Ninglin Advanced Materials Technology Company Limited, Nanjing 211505 (China)

    2016-04-01

    A novel drug carrier based on hydroxypropyl-β-cyclodextrin (HP-β-CD) modified carboxylated graphene oxide (GO-COOH) was designed to incorporate anti-cancer drug paclitaxel (PTX). The formulated nanomedicines were characterized by Fourier transform infrared spectroscopy (FTIR) and atomic force microscopy (AFM). Results showed that PTX can be incorporated into GO-COO-HP-β-CD nanospheres successfully, with an average diameter of about 100 nm. The solubility and stability of PTX-loaded GO-COO-HP-β-CD nanospheres in aqueous media were greatly enhanced compared with the untreated PTX. The results of hemolysis test demonstrated that the drug-loaded nanospheres were qualified with good blood compatibility for intravenous use. In vitro anti-tumor activity was measured and results demonstrated that the incorporation of PTX into the newly developed GO-COO-HP-β-CD carrier could confer significantly improved cytotoxicity to the nanosystem against tumor cells than single application of PTX. GO-COO-HP-β-CD nanospheres may represent a promising formulation platform for a broad range of therapeutic agent, especially those with poor solubility. - Highlights: • Hydroxypropyl-β-cyclodextrin (HP-β-CD) modified carboxylated graphene oxide (GO-COOH) was designed as a drug carrier. • The prepared PTX-loaded nanospheres can be dispersed in aqueous medium stably. • The GO-COO-HP-β-CD nanospheres are safe for blood-contact applications. • This newly developed PTX-delivery system could confer significantly improved cytotoxicity against tumor cells.

  15. [End therapeutic nihilism towards COPD].

    Science.gov (United States)

    Juergens, Uwe R

    2007-03-15

    Prevention of COPD requires appropriate patient education, especially of adolescents, as well as the establishment of an effective national health policy. The new GOLD guidelines represent the current standard of knowledge on the management of chronic, progressive, obstructive pulmonary diseases. It points out that COPD is avoidable and treatable,and hence, there is no reason for therapeutic nihilism. Chronic bronchitis preceding a progressive respiratory obstruction cannot be improved with the presently available respiratory therapeutics. For this reason, therapeutic measures concentrate on the avoidance of exacerbations, which are primarily responsible for the severity of the course of COPD.

  16. 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.

  17. Therapeutic hypothermia for acute stroke

    DEFF Research Database (Denmark)

    Olsen, Tom Skyhøj; Weber, Uno Jakob; Kammersgaard, Lars Peter

    2003-01-01

    Experimental evidence and clinical experience show that hypothermia protects the brain from damage during ischaemia. There is a growing hope that the prevention of fever in stroke will improve outcome and that hypothermia may be a therapeutic option for the treatment of stroke. Body temperature...... obvious therapeutic potential, hypothermia as a form of neuroprotection for stroke has been investigated in only a few very small studies. Therapeutic hypothermia is feasible in acute stroke but owing to serious side-effects--such as hypotension, cardiac arrhythmia, and pneumonia--it is still thought...

  18. Evaluation of dermatological effects of cosmetic formulations containing Saccharomyces cerevisiae extract and vitamins.

    Science.gov (United States)

    Gaspar, L R; Camargo, F B; Gianeti, M D; Maia Campos, P M B G

    2008-11-01

    Saccharomyces cerevisiae extract (SCE) is used in cosmetics since it can act in oxidative stress and improve skin conditions. This study investigated dermatological effects of cosmetic formulations containing SCE and/or vitamins A, C and E. The formulation studied was supplemented or not (F1: vehicle) with vitamins A, C and E esters (F2) or with SCE (F3) or with the combination of vitamins and SCE (F4). Formulations were patch tested on back skin of volunteers. For efficacy studies, formulations were applied on volunteers and transepidermal water loss (TEWL), skin moisture (SM), skin microrelief (SMR) and free radicals protection were analysed after 3h, 15 and 30 days of application. Volunteers were also asked about efficacy perception. It was observed that F4 provoked a slight erythema in one volunteer. All formulations enhanced forearm SM. Only F3 and F4 presented long term effects on SMR and showed higher texture values; F3 had the highest brightness values. Our results suggest that vitamins and SCE showed effects in SM and SMR. Only formulations containing SC had long term effects in the improvement of SMR. Thus, these kinds of evaluations are very important in cosmetics development to evaluate the best risk and benefit correlation.

  19. Glass formulation requirements for DWPF coupled operations using crystalline silicotitanates

    International Nuclear Information System (INIS)

    Harbour, J.R.; Andrews, M.K.

    1997-01-01

    The design basis DWPF flowsheet couples the vitrification of two waste streams: (1) a washed sludge and (2) a hydrolyzed sodium tetraphenylborate precipitate product, PHA. The PHA contains cesium-137 which had been precipitated from the tank supernate with sodium tetraphenylborate. Smaller amounts of strontium and plutonium adsorbed on sodium titanate are also present with the PHA feed. Currently, DWPF is running a sludge-only flowsheet while working towards solutions to the problems encountered with In Tank Precipitation (ITP). The sludge loading for the sludge-only flowsheet and for the anticipated coupled operations is 28 wt% on an oxide basis. For the coupled operation, it is essential to balance the treatment of the two waste streams such that no supernate remains after immobilization of all the sludge. An alternative to ITP and sodium titanate is the removal of Cs-137, Sr-90, and plutonium from the tank supernate by ion exchange using crystalline silicotitanate (CST). This material has been shown to effectively sorb these elements from the supernate. It is also known that CST sorbs plutonium. The loaded CST could then be immobilized with the sludge during vitrification. It has recently been demonstrated that CST loadings approaching 70 wt% for a CST-only glass can be achieved using a borosilicate glass formulation which can be processed by the DWPF melter. Initial efforts on coupled waste streams with simulated DWPF sludge show promise that a borosilicate glass formulation can incorporate both sludge and CST. This paper presents the bases for research efforts to develop a glass formulation which will incorporate sludge and CST at loadings appropriate for DWPF operation

  20. Formulation of lubricating grease using Beeswax thickener

    Science.gov (United States)

    Suhaila, N.; Japar, A.; Aizudin, M.; Aziz, A.; Najib Razali, Mohd

    2018-04-01

    The issues on environmental pollution has brought the industries to seek the alternative green solutions for lubricating grease formulation. The significant challenges in producing modified grease are in which considering the chosen thickener as one of the environmental friendly material. The main purposes of the current research were to formulate lubricant grease using different types of base oils and to study the effect of thickener on the formulated lubricant grease. Used oil and motor oil were used as the base oils for the grease preparation. Beeswax and Damar were used as thickener and additive. The grease is tested based on its consistency, stability and oil bleeding. The prepared greases achieved grease consistency of grade 2 and 3 except for grease with unfiltered used oil. Grease formulated with used oil and synthetic oil tend to harden and loss its lubricating ability under high temperature compared to motor oil’ grease. Grease modification using environmental friendly thickener were successfully formulated but it is considered as a low temperature grease as the beeswax have low melting point of 62°C-65°C.

  1. Bioequivalence assessment of two formulations of ibuprofen

    KAUST Repository

    Al-Talla, Zeyad

    2011-10-19

    Background: This study assessed the relative bioavailability of two formulations of ibuprofen. The first formulation was Doloraz , produced by Al-Razi Pharmaceutical Company, Amman, Jordan. The second forumulation was Brufen , manufactured by Boots Company, Nottingham, UK. Methods and results: A prestudy validation of ibuprofen demonstrated long-term stability, freeze-thaw stability, precision, and accuracy. Twenty-four healthy volunteers were enrolled in this study. After overnight fasting, the two formulations (test and reference) of ibuprofen (100 mg ibuprofen/5 mL suspension) were administered as a single dose on two treatment days separated by a one-week washout period. After dosing, serial blood samples were drawn for a period of 14 hours. Serum harvested from the blood samples was analyzed for the presence of ibuprofen by high-pressure liquid chromatography with ultraviolet detection. Pharmacokinetic parameters were determined from serum concentrations for both formulations. The 90% confidence intervals of the ln-transformed test/reference treatment ratios for peak plasma concentration and area under the concentration-time curve (AUC) parameters were found to be within the predetermined acceptable interval of 80%-125% set by the US Food and Drug Administration. Conclusion: Analysis of variance for peak plasma concentrations and AUC parameters showed no significant difference between the two formulations and, therefore, Doloraz was considered bioequivalent to Brufen. 2011 Al-Talla et al, publisher and licensee Dove Medical Press Ltd.

  2. Glass formulation for phase 1 high-level waste vitrification

    Energy Technology Data Exchange (ETDEWEB)

    Vienna, J.D.; Hrma, P.R.

    1996-04-01

    The purpose of this study is to provide potential glass formulations for prospective Phase 1 High-Level Waste (HLW) vitrification at Hanford. The results reported here will be used to aid in developing a Phase 1 HLW vitrification request for proposal (RFP) and facilitate the evaluation of ensuing proposals. The following factors were considered in the glass formulation effort: impact on total glass volume of requiring the vendor to process each of the tank compositions independently versus as a blend; effects of imposing typical values of B{sub 2}O{sub 3} content and waste loading in HLW borosilicate glasses as restrictions on the vendors (according to WAPS 1995, the typical values are 5--10 wt% B{sub 2}O{sub 3} and 20--40 wt% waste oxide loading); impacts of restricting the processing temperature to 1,150 C on eventual glass volume; and effects of caustic washing on any of the selected tank wastes relative to glass volume.

  3. Therapeutic potential of agmatine for CNS disorders.

    Science.gov (United States)

    Neis, Vivian B; Rosa, Priscila B; Olescowicz, Gislaine; Rodrigues, Ana Lúcia S

    2017-09-01

    Agmatine is a neuromodulator that regulates multiple neurotransmitters and signaling pathways. Several studies have focused on elucidating the mechanisms underlying the neuroprotective effects of this molecule, which seems to be mediated by a reduction in oxidative damage, neuroinflammation, and proapoptotic signaling. Since these events are implicated in acute and chronic excitotoxicity-related disorders (ischemia, epilepsy, traumatic brain injury, spinal cord injury, neurodegenerative, and psychiatric disorders) as well as in nociception, agmatine has been proposed as a therapeutic strategy for the treatment of central nervous system (CNS) disorders. Agmatine also stimulates the expression of trophic factors and adult neurogenesis, contributing to its ability to induce endogenous repair mechanisms. Therefore, considering its wide range of biological effects, this review summarizes the current knowledge about its protective and regenerative properties in the CNS. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Therapeutic neuroprotective agents for amyotrophic lateral sclerosis

    Science.gov (United States)

    Pandya, Rachna S.; Zhu, Haining; Li, Wei; Bowser, Robert; Friedlander, Robert M.

    2014-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal chronic neurodegenerative disease whose hallmark is proteinaceous, ubiquitinated, cytoplasmic inclusions in motor neurons and surrounding cells. Multiple mechanisms proposed as responsible for ALS pathogenesis include dysfunction of protein degradation, glutamate excitotoxicity, mitochondrial dysfunction, apoptosis, oxidative stress, and inflammation. It is therefore essential to gain a better understanding of the underlying disease etiology and search for neuroprotective agents that might delay disease onset, slow progression, prolong survival, and ultimately reduce the burden of disease. Because riluzole, the only Food and Drug Administration (FDA)-approved treatment, prolongs the ALS patient’s life by only 3 months, new therapeutic agents are urgently needed. In this review, we focus on studies of various small pharmacological compounds targeting the proposed pathogenic mechanisms of ALS and discuss their impact on disease progression. PMID:23864030

  5. Therapeutic hypothermia for acute liver failure

    DEFF Research Database (Denmark)

    Stravitz, R.T.; Larsen, Finn Stolze

    2009-01-01

    transplantation or spontaneous liver regeneration follows in short order. To buy time, the induction of therapeutic hypothermia (core temperature 32 degrees C-35 degrees C) has been shown to effectively bridge patients to transplant. Similar to the experience in patients with cerebral edema after other neurologic...... insults, hypothermia reduces cerebral edema and intracranial hypertension in patients with acute liver failure by decreasing splanchnic ammonia production, restoring normal regulation of cerebral hemodynamics, and lowering oxidative metabolism within the brain. Hypothermia may also ameliorate the degree...... of liver injury. Hypothermia has not been adequately studied for its safety and theoretically may increase the risk of infection, cardiac dysrhythmias, and bleeding, all complications independently associated with acute liver failure. Therefore, although an ample body of experimental and human data...

  6. Cyclodextrins as excipients in tablet formulations.

    Science.gov (United States)

    Conceição, Jaime; Adeoye, Oluwatomide; Cabral-Marques, Helena Maria; Lobo, José Manuel Sousa

    2018-04-22

    This paper aims to provide a critical review of cyclodextrins as excipients in tablet formulations, highlighting: (i) the principal pharmaceutical applications of cyclodextrins; (ii) the most relevant technological aspects in pharmaceutical formulation development; and (iii) the actual regulatory status of cyclodextrins. Moreover, several illustrative examples are presented. Cyclodextrins can be used as complexing excipients in tablet formulations for low-dose drugs. By contrast, for medium-dose drugs and/or when the complexation efficiency is low, the methods to enhance the complexation efficiency play a key part in reducing the cyclodextrin quantity. In addition, these compounds are used as fillers, disintegrants, binders and multifunctional direct compression excipients of the tablets. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. STRATEGY FORMULATION PROCESS AND INNOVATION PERFORMANCE NEXUS

    Directory of Open Access Journals (Sweden)

    Chijioke Nwachukwu

    2018-03-01

    Full Text Available The purpose of this study is to examine the link between strategy formulation process and innovation performance indicators in microfinance banks in Nigeria (MFBs. 100 employees of leading microfinance banks were randomly selected for this study. 80 questionnaires were returned but only 76 were found usable for the analysis. Regression analysis technique was used in examining the nature of the relationships of the variables and for hypotheses testing. The authors used exploratory factor analysis and Cronbach's alpha to test for the validity and reliability of the questionnaires. The results show that strategy formulation process has a positive effect on process innovation performance, product innovation performance and marketing innovation performance. Thus, all the three hypotheses tested were supported. The authors, therefore, concludes that a systematic strategy formulation process is necessary for firms to achieve and sustain process innovation performance, product innovation performance and marketing innovation performance. This study proposed suggestion for further studies.

  8. Formulating viscous hydrodynamics for large velocity gradients

    International Nuclear Information System (INIS)

    Pratt, Scott

    2008-01-01

    Viscous corrections to relativistic hydrodynamics, which are usually formulated for small velocity gradients, have recently been extended from Navier-Stokes formulations to a class of treatments based on Israel-Stewart equations. Israel-Stewart treatments, which treat the spatial components of the stress-energy tensor τ ij as dynamical objects, introduce new parameters, such as the relaxation times describing nonequilibrium behavior of the elements τ ij . By considering linear response theory and entropy constraints, we show how the additional parameters are related to fluctuations of τ ij . Furthermore, the Israel-Stewart parameters are analyzed for their ability to provide stable and physical solutions for sound waves. Finally, it is shown how these parameters, which are naturally described by correlation functions in real time, might be constrained by lattice calculations, which are based on path-integral formulations in imaginary time

  9. Design Considerations in Therapeutic Exergaming

    OpenAIRE

    Doyle, Julie; Kelly, Daniel; Caulfield, B.

    2011-01-01

    In this paper we discuss the importance of feedback in therapeutic exergaming. It is widely believed that exergaming benefits the patient in terms of encouraging adherence and boosting the patient’s confidence of correct execution and feedback is essential in achieving these. However, feedback and in particular visual feedback, may also have potential negative effects on the quality of the exercise. We describe in this paper a prototype single-sensor therapeutic exergame that we have develope...

  10. Evaluation of therapeutic patient education

    OpenAIRE

    D'Ivernois , Jean-François; Gagnayre , Rémi; Assal , Jean-Philippe; Golay , Alain; Libion , France; Deccache , Alain

    2006-01-01

    9 pages; These guidelines mainly focus on the principles of evaluating Therapeutic Patient Education; Over the past thirty years, therapeutic patient education (TPE) has become an essential part of the treatment of long-term diseases. Evaluations of this new practice are expected, and are sometimes imposed according to protocols and criteria that do not always reflect the complexity of changes taking place within patients and healthcare providers. Sometimes, expected results are not achieved ...

  11. 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 ...

  12. Formulation and stability testing of photolabile drugs.

    Science.gov (United States)

    Tønnesen, H H

    2001-08-28

    Exposure of a drug to irradiation can influence the stability of the formulation, leading to changes in the physicochemical properties of the product. The influence of excipients of frequently used stabilizers is often difficult to predict and, therefore, stability testing of the final preparation is important. The selection of a protective packaging must be based on knowledge about the wavelength causing the instability. Details on drug photoreactivity will also be helpful in order to minimize side-effects and/or optimize drug targeting by developing photoresponsive drug delivery systems. This review focuses on practical problems related to formulation and stability testing of photolabile drugs.

  13. Controlled-release tablet formulation of isoniazid.

    Science.gov (United States)

    Jain, N K; Kulkarni, K; Talwar, N

    1992-04-01

    Guar (GG) and Karaya gums (KG) alone and in combination with hydroxy-propylmethylcellulose (HPMC) were evaluated as release retarding materials to formulate a controlled-release tablet dosage form of isoniazid (1). In vitro release of 1 from tablets followed non-Fickian release profile with rapid initial release. Urinary excretion studies in normal subjects showed steady-state levels of 1 for 13 h. In vitro and in vivo data correlated (r = 0.9794). The studies suggested the potentiality of GG and KG as release retarding materials in formulating controlled-release tablet dosage forms of 1.

  14. An exact approach for aggregated formulations

    DEFF Research Database (Denmark)

    Gamst, Mette; Spoorendonk, Simon

    Aggregating formulations is a powerful approach for transforming problems into taking more tractable forms. Aggregated formulations can, though, have drawbacks: some information may get lost in the aggregation and { put in a branch-and-bound context { branching may become very di_cult and even....... The paper includes general considerations on types of problems for which the method is of particular interest. Furthermore, we prove the correctness of the procedure and consider how to include extensions such as cutting planes and advanced branching strategies....

  15. Quaternionic formulation of the exact parity model

    Energy Technology Data Exchange (ETDEWEB)

    Brumby, S.P.; Foot, R.; Volkas, R.R.

    1996-02-28

    The exact parity model (EPM) is a simple extension of the standard model which reinstates parity invariance as an unbroken symmetry of nature. The mirror matter sector of the model can interact with ordinary matter through gauge boson mixing, Higgs boson mixing and, if neutrinos are massive, through neutrino mixing. The last effect has experimental support through the observed solar and atmospheric neutrino anomalies. In the paper it is shown that the exact parity model can be formulated in a quaternionic framework. This suggests that the idea of mirror matter and exact parity may have profound implications for the mathematical formulation of quantum theory. 13 refs.

  16. Quaternionic formulation of the exact parity model

    International Nuclear Information System (INIS)

    Brumby, S.P.; Foot, R.; Volkas, R.R.

    1996-01-01

    The exact parity model (EPM) is a simple extension of the standard model which reinstates parity invariance as an unbroken symmetry of nature. The mirror matter sector of the model can interact with ordinary matter through gauge boson mixing, Higgs boson mixing and, if neutrinos are massive, through neutrino mixing. The last effect has experimental support through the observed solar and atmospheric neutrino anomalies. In the paper it is shown that the exact parity model can be formulated in a quaternionic framework. This suggests that the idea of mirror matter and exact parity may have profound implications for the mathematical formulation of quantum theory. 13 refs

  17. Formulation, stabilisation and encapsulation of bacteriophage for phage therapy.

    Science.gov (United States)

    Malik, Danish J; Sokolov, Ilya J; Vinner, Gurinder K; Mancuso, Francesco; Cinquerrui, Salvatore; Vladisavljevic, Goran T; Clokie, Martha R J; Garton, Natalie J; Stapley, Andrew G F; Kirpichnikova, Anna

    2017-11-01

    Against a backdrop of global antibiotic resistance and increasing awareness of the importance of the human microbiota, there has been resurgent interest in the potential use of bacteriophages for therapeutic purposes, known as phage therapy. A number of phage therapy phase I and II clinical trials have concluded, and shown phages don't present significant adverse safety concerns. These clinical trials used simple phage suspensions without any formulation and phage stability was of secondary concern. Phages have a limited stability in solution, and undergo a significant drop in phage titre during processing and storage which is unacceptable if phages are to become regulated pharmaceuticals, where stable dosage and well defined pharmacokinetics and pharmacodynamics are de rigueur. Animal studies have shown that the efficacy of phage therapy outcomes depend on the phage concentration (i.e. the dose) delivered at the site of infection, and their ability to target and kill bacteria, arresting bacterial growth and clearing the infection. In addition, in vitro and animal studies have shown the importance of using phage cocktails rather than single phage preparations to achieve better therapy outcomes. The in vivo reduction of phage concentration due to interactions with host antibodies or other clearance mechanisms may necessitate repeated dosing of phages, or sustained release approaches. Modelling of phage-bacterium population dynamics reinforces these points. Surprisingly little attention has been devoted to the effect of formulation on phage therapy outcomes, given the need for phage cocktails, where each phage within a cocktail may require significantly different formulation to retain a high enough infective dose. This review firstly looks at the clinical needs and challenges (informed through a review of key animal studies evaluating phage therapy) associated with treatment of acute and chronic infections and the drivers for phage encapsulation. An important driver

  18. Impact of Oxidative Stress in Fetal Programming

    OpenAIRE

    Thompson, Loren P.; Al-Hasan, Yazan

    2012-01-01

    Intrauterine stress induces increased risk of adult disease through fetal programming mechanisms. Oxidative stress can be generated by several conditions, such as, prenatal hypoxia, maternal under- and overnutrition, and excessive glucocorticoid exposure. The role of oxidant molecules as signaling factors in fetal programming via epigenetic mechanisms is discussed. By linking oxidative stress with dysregulation of specific target genes, we may be able to develop therapeutic strategies that pr...

  19. Impact of Oxidative Stress in Fetal Programming

    Directory of Open Access Journals (Sweden)

    Loren P. Thompson

    2012-01-01

    Full Text Available Intrauterine stress induces increased risk of adult disease through fetal programming mechanisms. Oxidative stress can be generated by several conditions, such as, prenatal hypoxia, maternal under- and overnutrition, and excessive glucocorticoid exposure. The role of oxidant molecules as signaling factors in fetal programming via epigenetic mechanisms is discussed. By linking oxidative stress with dysregulation of specific target genes, we may be able to develop therapeutic strategies that protect against organ dysfunction in the programmed offspring.

  20. Applications of inorganic nanoparticles as therapeutic agents

    International Nuclear Information System (INIS)

    Kim, Taeho; Hyeon, Taeghwan

    2014-01-01

    During the last decade, various functional nanostructured materials with interesting optical, magnetic, mechanical and chemical properties have been extensively applied to biomedical areas including imaging, diagnosis and therapy. In therapeutics, most research has focused on the application of nanoparticles as potential delivery vehicles for drugs and genes, because nanoparticles in the size range of 2–100 nm can interact with biological systems at the molecular level, and allow targeted delivery and passage through biological barriers. Recent investigations have even revealed that several kinds of nanomaterials are intrinsically therapeutic. Not only can they passively interact with cells, but they can also actively mediate molecular processes to regulate cell functions. This can be seen in the treatment of cancer via anti-angiogenic mechanisms as well as the treatment of neurodegenerative diseases by effectively controlling oxidative stress. This review will present recent applications of inorganic nanoparticles as therapeutic agents in the treatment of disease. (topical review)

  1. Catalytic oxidation using nitrous oxide

    Directory of Open Access Journals (Sweden)

    Juan Carlos Beltran-Prieto

    2017-01-01

    Full Text Available Nitrous oxide is a very inert gas used generally as oxidant as it offers some advantage compared with other oxidants such as O2 but a considerably higher temperature (> 526 °C is often required. For particular cases such as the oxidation of sugar alcohols, especially for the oxidation of primary alcohols to aldehydes, N2O has the advantage over O2 of a higher reaction selectivity. In the present paper we present the modelling of oxidation reaction of sugar alcohols using an oxidizing agent in low concentrations, which is important to suppress subsequent oxidation reactions due to the very low residual concentrations of the oxidizing agent. For orientation experiments we chose nitrous oxide generated by thermal decomposition of ammonium nitrate. Kinetic modeling of the reaction was performed after determination of the differential equations that describe the system under study.

  2. Water-soluble Coenzyme Q10 formulation (Q-ter) promotes outer hair cell survival in a guinea pig model of noise induced hearing loss (NIHL).

    Science.gov (United States)

    Fetoni, Anna Rita; Piacentini, Roberto; Fiorita, Antonella; Paludetti, Gaetano; Troiani, Diana

    2009-02-27

    The mitochondrial respiratory chain is a powerful source of reactive oxygen species (ROS) also in noise induced hearing loss (NIHL) and anti-oxidants and free-radicals scavengers have been shown to attenuate the damage. Coenzyme Q(10) (CoQ(10)) or ubiquinone has a bioenergetic role as a component of the mithocondrial respiratory chain, it inhibits mitochondrial lipid peroxidation, inducing ATP production and it is involved in ROS removal and prevention of oxidative stress-induced apoptosis. However the therapeutic application of CoQ(10) is limited by the lack of solubility and poor bio- availability, therefore it is a challenge to improve its water solubility in order to ameliorate the efficacy in tissues and fluids. This study was conducted in a model of acoustic trauma in the guinea pig where the effectiveness of CoQ(10) was compared with a soluble formulation of CoQ(10) (multicomposite CoQ(10) Terclatrate, Q-ter) given intraperitoneally 1 h before and once daily for 3 days after pure tone noise exposure (6 kHz for 1 h at 120 dB SPL). Functional and morphological studies were carried out by measuring auditory brainstem responses, scanning electron microscopy for hair cell loss count, active caspase 3 staining and terminal deoxynucleotidyl transferase-mediated dUTP labelling assay in order to identify initial signs of apoptosis. Treatments decreased active caspase 3 expression and the number of apoptotic cells, but animals injected with Q-ter showed a greater degree of activity in preventing apoptosis and thus in improving hearing. These data confirm that solubility of Coenzyme Q(10) improves the ability of CoQ(10) in preventing oxidative injuries that result from mitochondrial dysfunction.

  3. 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.

  4. Screening of mucoadhesive vaginal gel formulations

    Directory of Open Access Journals (Sweden)

    Ana Ochoa Andrade

    2014-12-01

    Full Text Available Rational design of vaginal drug delivery formulations requires special attention to vehicle properties that optimize vaginal coating and retention. The aim of the present work was to perform a screening of mucoadhesive vaginal gels formulated with carbomer or carrageenan in binary combination with a second polymer (carbomer, guar or xanthan gum. The gels were characterised using in vitroadhesion, spreadability and leakage potential studies, as well as rheological measurements (stress and frequency sweep tests and the effect of dilution with simulated vaginal fluid (SVF on spreadability. Results were analysed using analysis of variance and multiple factor analysis. The combination of polymers enhanced adhesion of both primary gelling agents, carbomer and carrageenan. From the rheological point of view all formulations presented a similar behaviour, prevalently elastic and characterised by loss tangent values well below 1. No correlation between rheological and adhesion behaviour was found. Carbomer and carrageenan gels containing the highest percentage of xanthan gum displayed good in vitro mucoadhesion and spreadability, minimal leakage potential and high resistance to dilution. The positive results obtained with carrageenan-xanthan gum-based gels can encourage the use of natural biocompatible adjuvants in the composition of vaginal products, a formulation field that is currently under the synthetic domain.

  5. Formulation of Sodium Alginate Nanospheres Containing ...

    African Journals Online (AJOL)

    Purpose: The aim of this work was to formulate sodium alginate nanospheres of amphotericin B by controlled gellification method and to evaluate the role of the nanospheres as a “passive carrier” in targeted antifungal therapy. Methods: Sodium alginate nanospheres of amphotericin B were prepared by controlled ...

  6. [Optimization of formulations for dietetic pastry products].

    Science.gov (United States)

    Villarroel, M; Uquiche, E; Brito, G; Cancino, M

    2000-03-01

    Optimized formulations of dietetic pastry products such as cake and sponge cake premixes were formulated using the surface response methodology. % Emulsifier agent and baking time were the selected independent variables for cake, as well as % emulsifier agent % chlorinated flour the variables selected for sponge cake. Three different level of each variable summing up thirteen experimental formulae of each product were assessed to optimize the variables that could have some influence in the sensory characteristics of these dietetic products. The total sensory quality was determined for both dietetic products using the composite scoring test and a panel of 18 trained judges. Looking at the contour graphic and considering economic aspects the best combination of variables for cake formulation was 2% emulsifier agent and 48 minutes for baking time, With respect to sponge cake, the best combination was 6% emulsifier agent and 48% chlorinated flour. Shelf life studies showed that both dietetic formulations remained stable during storage conditions of 75 days at 30 degrees C. During this period, significant differences in sensory characteristics were not found (p pastry products had good acceptability, and open up marketing opportunities for new products with potential health benefits to consumers.

  7. Facile Colorimetric Determination of Duloxetine in Formulations ...

    African Journals Online (AJOL)

    ... the determination of duloxetine hydrochloride (DX). Methods: Ion-pair spectrophotometric method was employed for the determination of duloxetine hydrochloride (DX) in bulk and pharmaceutical formulations using acidic dye methyl orange (MO) as ion-pairing agent at pH 4 (phthalate buffer). The yellow ion-pair complex ...

  8. Engaged Problem Formulation in IS Research

    DEFF Research Database (Denmark)

    Nielsen, Peter Axel; Persson, John Stouby

    2016-01-01

    problems requires a more substantial engagement with the different stakeholders, especially when their problems are ill structured and situated in complex organizational settings. On this basis, we present an engaged approach to formulating IS problems with, not for, IS practitioners. We have come...

  9. Effects of Methionine Containing Paracetamol Formulation on ...

    African Journals Online (AJOL)

    Effects of Methionine Containing Paracetamol Formulation on Serum Vitamins and Trace Elements in Male Rats. AA Iyanda, JI Anetor, DP Oparinde, FAA Adeniyi. Abstract. Methionine is an effective antidote in the treatment of paracetamol-induced toxicity but at large doses it has been reported to induce or aggravate a ...

  10. State-Space Formulation for Circuit Analysis

    Science.gov (United States)

    Martinez-Marin, T.

    2010-01-01

    This paper presents a new state-space approach for temporal analysis of electrical circuits. The method systematically obtains the state-space formulation of nondegenerate linear networks without using concepts of topology. It employs nodal/mesh systematic analysis to reduce the number of undesired variables. This approach helps students to…

  11. Yang-Mills formulation of interacting strings

    International Nuclear Information System (INIS)

    Chan Hongmo; Tsou Sheungtsun

    1988-06-01

    A suggestion that the theory of interacting open bosonic string be reformulated as a generalised Yang-Mills theory is further elucidated. Moreover, a serious reservation regarding the ordering of operators in the earlier 'proof' of equivalence between the new and standard formulations is now removed. (author)

  12. Initial value formulation of higher derivative gravity

    International Nuclear Information System (INIS)

    Noakes, D.R.

    1983-01-01

    The initial value problem is considered for the conformally coupled scalar field and higher derivative gravity, by expressing the equations of each theory in harmonic coordinates. For each theory it is shown that the (vacuum) equations can take the form of a diagonal hyperbolic system with constraints on the initial data. Consequently these theories possess well-posed initial value formulations

  13. Release Properties of Paracetamol Granulationa Formulated with ...

    African Journals Online (AJOL)

    Theobroma cacao gum, TCG was derived as a dry powder from fresh fruits of Theobroma cacao. Various granulations of paracetamol were prepared with TCG at the concentrations of 0.5 – 4% w/w. Similar formulations were prepared using sodium carboxymethyl cellulose, SCMC and acacia gums as standards. In each ...

  14. Probabilites in the general boundary formulation

    Energy Technology Data Exchange (ETDEWEB)

    Oeckl, Robert [Instituto de Matematicas, UNAM, Campus Morelia, C.P. 58190, Morelia, Michoacan (Mexico)

    2007-05-15

    We give an introductory account of the general boundary formulation of quantum theory. We refine its probability interpretation and emphasize a conceptual and historical perspective. We give motivations from quantum gravity and illustrate them with a scenario for describing gravitons in quantum gravity.

  15. On fictitious domain formulations for Maxwell's equations

    DEFF Research Database (Denmark)

    Dahmen, W.; Jensen, Torben Klint; Urban, K.

    2003-01-01

    We consider fictitious domain-Lagrange multiplier formulations for variational problems in the space H(curl: Omega) derived from Maxwell's equations. Boundary conditions and the divergence constraint are imposed weakly by using Lagrange multipliers. Both the time dependent and time harmonic formu...

  16. Necessity of rethinking oral pediatric formulations

    DEFF Research Database (Denmark)

    Bar-Shalom, Daniel

    2014-01-01

    by all patient groups, is needed, and an automated compounding concept is proposed. The finishing of the formulation is done at the dispensing pharmacy using an automated process. The individual components (pudding-like carrier, microencapsulated drug, and the dispensing robot and its software...

  17. Lagrangian formulation of classical BMT-theory

    International Nuclear Information System (INIS)

    Pupasov-Maksimov, Andrey; Deriglazov, Alexei; Guzman, Walberto

    2013-01-01

    Full text: The most popular classical theory of electron has been formulated by Bargmann, Michel and Telegdi (BMT) in 1959. The BMT equations give classical relativistic description of a charged particle with spin and anomalous magnetic momentum moving in homogeneous electro-magnetic field. This allows to study spin dynamics of polarized beams in uniform fields. In particular, first experimental measurements of muon anomalous magnetic momentum were done using changing of helicity predicted by BMT equations. Surprisingly enough, a systematic formulation and the analysis of the BMT theory are absent in literature. In the present work we particularly fill this gap by deducing Lagrangian formulation (variational problem) for BMT equations. Various equivalent forms of Lagrangian will be discussed in details. An advantage of the obtained classical model is that the Lagrangian action describes a relativistic spinning particle without Grassmann variables, for both free and interacting cases. This implies also the possibility of canonical quantization. In the interacting case, an arbitrary electromagnetic background may be considered, which generalizes the BMT theory formulated to the case of homogeneous fields. The classical model has two local symmetries, which gives an interesting example of constrained classical dynamics. It is surprising, that the case of vanishing anomalous part of the magnetic momentum is naturally highlighted in our construction. (author)

  18. A parcel formulation for Hamiltonian layer models

    NARCIS (Netherlands)

    Bokhove, Onno; Oliver, M.

    Starting from the three-dimensional hydrostatic primitive equations, we derive Hamiltonian N-layer models with isentropic tropospheric and isentropic or isothermal stratospheric layers. Our construction employs a new parcel Hamiltonian formulation which describes the fluid as a continuum of

  19. Clinical pharmacology of novel anticancer drug formulations

    NARCIS (Netherlands)

    Stuurman, F.E.

    2013-01-01

    Studies outlined in this thesis describe the impact of drug formulations on pharmacology of anticancer drugs. It consists of four parts and starts with a review describing the mechanisms of low oral bioavailability of anti-cancer drugs and strategies for improvement of the bioavailability. The

  20. Comparative evaluation of organic formulations of Pseudomonas ...

    African Journals Online (AJOL)

    An experiment was conducted in the laboratory and farm of the Department of Biotechnology, Gauhati University, to explore the potentiality of various organic formulations of Pseudomonas fluorescens (Pf) and to manage bacterial wilt disease of brinjal (Solanum melongena L.) under local conditions. Different organic ...

  1. Formulation and evaluation and terbutaline sulphate and ...

    African Journals Online (AJOL)

    We report the use of low rugosity lactose, product of controlled crystallization of this carrier, in the formulation of terbutaline sulphate and beclomethasone dipropionate dry powder inhalers. The deposition patterns obtained with inhalation mixtures consisting of the modified lactose and each of the micronised drugs ...

  2. Development and Evaluation of Topical Gabapentin Formulations

    Directory of Open Access Journals (Sweden)

    Christopher J. Martin

    2017-08-01

    Full Text Available Topical delivery of gabapentin is desirable to treat peripheral neuropathic pain conditions whilst avoiding systemic side effects. To date, reports of topical gabapentin delivery in vitro have been variable and dependent on the skin model employed, primarily involving rodent and porcine models. In this study a variety of topical gabapentin formulations were investigated, including Carbopol® hydrogels containing various permeation enhancers, and a range of proprietary bases including a compounded Lipoderm® formulation; furthermore microneedle facilitated delivery was used as a positive control. Critically, permeation of gabapentin across a human epidermal membrane in vitro was assessed using Franz-type diffusion cells. Subsequently this data was contextualised within the wider scope of the literature. Although reports of topical gabapentin delivery have been shown to vary, largely dependent upon the skin model used, this study demonstrated that 6% (w/w gabapentin 0.75% (w/w Carbopol® hydrogels containing 5% (w/w DMSO or 70% (w/w ethanol and a compounded 10% (w/w gabapentin Lipoderm® formulation were able to facilitate permeation of the molecule across human skin. Further pre-clinical and clinical studies are required to investigate the topical delivery performance and pharmacodynamic actions of prospective formulations.

  3. Development and Evaluation of Topical Gabapentin Formulations

    Science.gov (United States)

    Alcock, Natalie; Hiom, Sarah; Birchall, James C.

    2017-01-01

    Topical delivery of gabapentin is desirable to treat peripheral neuropathic pain conditions whilst avoiding systemic side effects. To date, reports of topical gabapentin delivery in vitro have been variable and dependent on the skin model employed, primarily involving rodent and porcine models. In this study a variety of topical gabapentin formulations were investigated, including Carbopol® hydrogels containing various permeation enhancers, and a range of proprietary bases including a compounded Lipoderm® formulation; furthermore microneedle facilitated delivery was used as a positive control. Critically, permeation of gabapentin across a human epidermal membrane in vitro was assessed using Franz-type diffusion cells. Subsequently this data was contextualised within the wider scope of the literature. Although reports of topical gabapentin delivery have been shown to vary, largely dependent upon the skin model used, this study demonstrated that 6% (w/w) gabapentin 0.75% (w/w) Carbopol® hydrogels containing 5% (w/w) DMSO or 70% (w/w) ethanol and a compounded 10% (w/w) gabapentin Lipoderm® formulation were able to facilitate permeation of the molecule across human skin. Further pre-clinical and clinical studies are required to investigate the topical delivery performance and pharmacodynamic actions of prospective formulations. PMID:28867811

  4. Engaged Problem Formulation in IS Research

    DEFF Research Database (Denmark)

    Nielsen, Peter Axel; Persson, John Stouby

    2016-01-01

    “Is this the problem?”: the question that haunts many information systems (IS) researchers when they pursue work relevant to both practice and research. Nevertheless, a deliberate answer to this question requires more than simply asking the involved IS practitioners. Deliberately formulating...

  5. Kit systems for granulated decontamination formulations

    Science.gov (United States)

    Tucker, Mark D.

    2010-07-06

    A decontamination formulation and method of making that neutralizes the adverse health effects of both chemical and biological compounds, especially chemical warfare (CW) and biological warfare (BW) agents, and toxic industrial chemicals. The formulation provides solubilizing compounds that serve to effectively render the chemical and biological compounds, particularly CW and BW compounds, susceptible to attack, and at least one reactive compound that serves to attack (and detoxify or kill) the compound. The formulation includes at least one solubilizing agent, a reactive compound, a sorbent additive, and water. A highly adsorbent sorbent additive (e.g., amorphous silica, sorbitol, mannitol, etc.) is used to "dry out" one or more liquid ingredients into a dry, free-flowing powder that has an extended shelf life, and is more convenient to handle and mix in the field. The formulation can be pre-mixed and pre-packaged as a multi-part kit system, where one or more of the parts are packaged in a powdered, granulated form for ease of handling and mixing in the field.

  6. Application of UV Imaging in Formulation Development.

    Science.gov (United States)

    Sun, Yu; Østergaard, Jesper

    2017-05-01

    Efficient drug delivery is dependent on the drug substance dissolving in the body fluids, being released from dosage forms and transported to the site of action. A fundamental understanding of the interplay between the physicochemical properties of the active compound and pharmaceutical excipients defining formulation behavior after exposure to the aqueous environments and pharmaceutical performance is critical in pharmaceutical development, manufacturing and quality control of drugs. UV imaging has been explored as a tool for qualitative and quantitative characterization of drug dissolution and release with the characteristic feature of providing real-time visualization of the solution phase drug transport in the vicinity of the formulation. Events occurring during drug dissolution and release, such as polymer swelling, drug precipitation/recrystallization, or solvent-mediated phase transitions related to the structural properties of the drug substance or formulation can be monitored. UV imaging is a non-intrusive and simple-to-operate analytical technique which holds potential for providing a mechanistic foundation for formulation development. This review aims to cover applications of UV imaging in the early and late phase pharmaceutical development with a special focus on the relation between structural properties and performance. Potential areas of future advancement and application are also discussed.

  7. Transendothelial Transport and Its Role in Therapeutics

    Science.gov (United States)

    Upadhyay, Ravi Kant

    2014-01-01

    Present review paper highlights role of BBB in endothelial transport of various substances into the brain. More specifically, permeability functions of BBB in transendothelial transport of various substances such as metabolic fuels, ethanol, amino acids, proteins, peptides, lipids, vitamins, neurotransmitters, monocarbxylic acids, gases, water, and minerals in the peripheral circulation and into the brain have been widely explained. In addition, roles of various receptors, ATP powered pumps, channels, and transporters in transport of vital molecules in maintenance of homeostasis and normal body functions have been described in detail. Major role of integral membrane proteins, carriers, or transporters in drug transport is highlighted. Both diffusion and carrier mediated transport mechanisms which facilitate molecular trafficking through transcellular route to maintain influx and outflux of important nutrients and metabolic substances are elucidated. Present review paper aims to emphasize role of important transport systems with their recent advancements in CNS protection mainly for providing a rapid clinical aid to patients. This review also suggests requirement of new well-designed therapeutic strategies mainly potential techniques, appropriate drug formulations, and new transport systems for quick, easy, and safe delivery of drugs across blood brain barrier to save the life of tumor and virus infected patients. PMID:27355037

  8. Targeted Therapeutic Nanoparticles: An Immense Promise to Fight against Cancer

    Directory of Open Access Journals (Sweden)

    Sheikh Tasnim Jahan

    2017-01-01

    Full Text Available In nanomedicine, targeted therapeutic nanoparticle (NP is a virtual outcome of nanotechnology taking the advantage of cancer propagation pattern. Tying up all elements such as therapeutic or imaging agent, targeting ligand, and cross-linking agent with the NPs is the key concept to deliver the payload selectively where it intends to reach. The microenvironment of tumor tissues in lymphatic vessels can also help targeted NPs to achieve their anticipated accumulation depending on the formulation objectives. This review accumulates the application of poly(lactic-co-glycolic acid (PLGA and polyethylene glycol (PEG based NP systems, with a specific perspective in cancer. Nowadays, PLGA, PEG, or their combinations are the mostly used polymers to serve the purpose of targeted therapeutic NPs. Their unique physicochemical properties along with their biological activities are also discussed. Depending on the biological effects from parameters associated with existing NPs, several advantages and limitations have been explored in teaming up all the essential facts to give birth to targeted therapeutic NPs. Therefore, the current article will provide a comprehensive review of various approaches to fabricate a targeted system to achieve appropriate physicochemical properties. Based on such findings, researchers can realize the benefits and challenges for the next generation of delivery systems.

  9. Bioequivalence assessment of two formulations of ibuprofen

    Directory of Open Access Journals (Sweden)

    Al-Talla ZA

    2011-10-01

    Full Text Available Zeyad A Al-Talla1, Sabah H Akrawi2, Luke T Tolley3, Salim H Sioud1, Mohammed F Zaater4, Abdul-Hamid M Emwas1 1Analytical and NMR Core Laboratories, King Abdullah University of Science and Technology, Thuwal, Kingdom of Saudia Arabia; 2College of Pharmacy, Al-Ain University, Al-Ain, United Arab Emirates; 3Department of Chemistry and Biochemistry, Southern Illinois University Carbondale, Carbondale, IL, USA; 4Department of Chemistry, Jordan University of Science and Technology, Jordan University of Science and Technology, Irbid, Jordan Background: This study assessed the relative bioavailability of two formulations of ibuprofen. The first formulation was Doloraz®, produced by Al-Razi Pharmaceutical Company, Amman, Jordan. The second forumulation was Brufen®, manufactured by Boots Company, Nottingham, UK. Methods and results: A prestudy validation of ibuprofen demonstrated long-term stability, freeze-thaw stability, precision, and accuracy. Twenty-four healthy volunteers were enrolled in this study. After overnight fasting, the two formulations (test and reference of ibuprofen (100 mg ibuprofen/5 mL suspension were administered as a single dose on two treatment days separated by a one-week washout period. After dosing, serial blood samples were drawn for a period of 14 hours. Serum harvested from the blood samples was analyzed for the presence of ibuprofen by high-pressure liquid chromatography with ultraviolet detection. Pharmacokinetic parameters were determined from serum concentrations for both formulations. The 90% confidence intervals of the ln-transformed test/reference treatment ratios for peak plasma concentration and area under the concentration-time curve (AUC parameters were found to be within the predetermined acceptable interval of 80%–125% set by the US Food and Drug Administration. Conclusion: Analysis of variance for peak plasma concentrations and AUC parameters showed no significant difference between the two formulations and

  10. Some aspects of the formulation of alginate dental impression materials--setting characteristics and mechanical properties.

    Science.gov (United States)

    Nallamuthu, Navina A; Braden, Michael; Patel, Mangala P

    2012-07-01

    To study the role of the various components of alginate dental impression materials. Experimental materials were formulated and their physical properties characterized and compared to commercially available counterparts (Neocolloid, Palgat Plus and Blueprint Cremix). Properties examined were: dimensional stability and weight change in water and artificial saliva; setting behavior; Shore A hardness and tear energy. The role of magnesium oxide was also investigated. Weight changes in water and artificial saliva can be attributed to an initial thermodynamic potential owing to the ionic content of the alginate, causing water to diffuse into the material. Water is then driven back out following a reversal of this potential. Hardness results for experimental materials were within the range obtained from the commercial materials. The hardness value for an experimental formulation that did not contain magnesium oxide was lower than values from the other experimental materials that did. Tear energies for all three experimental materials were greater than those of the commercial products. There were statistically significant differences between the two experimental materials that contained magnesium oxide and one that did not. With regard to setting time, statistically significant differences were seen between commercial materials and two of the experimental materials. The experimental material that did not contain magnesium oxide had a considerably longer setting time than all of the other materials tested. The key role of magnesium oxide in the setting reaction and the effect on hardness have been demonstrated and discussed. Copyright © 2012 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

  11. Evolving herbal formulations in management of dengue fever.

    Science.gov (United States)

    Singh, Pawan Kumar; Rawat, Pooja

    Dengue is endemic in more than 100 countries and it is estimated that annually above 390 million infections occur globally. During the period between 1996-2015, a massive increase of more than 500 per cent has been recorded in number of dengue cases reported in India. Till date, there are no specific globally accepted treatments for dengue fever in any system of medicine. Dengue does not cause very high mortality if properly handled and is currently being managed by clinicians through various adjuvant and alternative therapeutic options. Various plant based preparations have been used in different parts of India for combating dengue and are simultaneously also being scientifically validated by researchers. However, number of such scientific validation studies on phytomedicines are very less in India. Out of twenty-two plants reported against dengue, only four have been studied scientifically. Azadirachta indica, Carica papaya, Hippophae rhamnoides and Cissampelos pareira extracts were found effective and demonstrated improvement in clinical symptoms and direct inhibitory effect on dengue virus. C. papaya clinical trial showed increase in platelet count and faster recovery. These plants may be explored further as probable candidates for drug discovery against dengue. There is a need to search more such herbal formulations, which are being practiced at local level, document properly and validate them scientifically to confirm efficacy, mechanistic action and safety, before use. The herbal formulations being used by communities are the low hanging fruits which may provide alternative or adjuvant therapy if proper validation, value addition and product development steps are followed. This paper aims to review the recent status of dengue cases, deaths and evolving curative herbal solutions adapted and reported from India to combat the disease. Copyright © 2017 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Published by Elsevier B.V. All rights

  12. [Diabetic retinopathy: pathogenesis and therapeutic implications].

    Science.gov (United States)

    Pelikánová, Terezie

    Diabetic retinopathy (DR) develops in patients with both type 1 and type 2 diabetes and is the major cause of vision loss and blindness in the working population. The main risk factor of DR is hyperglycemia accompanied by enhanced mitochondrial production of reactive oxygen species and oxidative stress, formation of advanced glycation end products (AGE) and hexosamines, increase in polyol metabolism of glucose. The severity of vascular injury depends on the individual genetic background and is modified by other epigenetic, metabolic and haemodynamic factors, including hypertension, dyslipidemia and oxidative stress. In diabetes, damage to the retina occurs in the vasculature (endothelial cells and pericytes), neurons and glia, pigment epithelial cells and infiltrating immunocompetent cells: monocytes, granulocytes, lymfocytes. These activated cells change the production pattern of a number of mediators such as growth factors, proinflammatory cytokines, vasoactive molecules, coagulation factors and adhesion molecules resulting in increased blood flow, increased capillary permeability, proliferation of extracellular matrix and thickening of basal membranes, altered cell turnover (apoptosis, proliferation, hypertrophy), procoagulant and proaggregant pattern, and finally in angiogenesis and tissue remodelling. Brain, liver, adipose tissue, GUT, skeletal muscle and other tissues could be another source of mediators. Therapeutic approaches used for patients with or at risk for diabetic retinopathy include drug therapy to reduce modifiable risk factors, laser photocoagulation, intravitreous administration of anti-VEGF agents/steroids and intraocular surgery. Screening plays an important role in early detection and intervention to prevent the progression of diabetic retinopathy. Described insights into pathophysiological mechanisms responsible for DR, could help in the development of more targeted approach for prevention and treatment of diabetic retinopathy. anti

  13. Topical formulations with superoxide dismutase: influence of formulation composition on physical stability and enzymatic activity.

    Science.gov (United States)

    Di Mambro, Valéria M; Borin, Maria F; Fonseca, Maria J V

    2003-04-24

    Three different topical formulations were supplemented with superoxide dismutase (SOD) and evaluated concerning physical and chemical stabilities in order to determine the most stable formulation that would maintain SOD activity. Physical stability was evaluated by storing the formulation at room temperature, and at 37 and 45 degrees C for 28 days. Samples were collected at 7-day intervals for assessment of rheological behavior. Chemical stability was evaluated by the measurement of enzymatic activity in formulations stored at room temperature and at 45 degrees C for 75 days. The formulations showed a pseudoplastic behavior, with a flow index of less than 1. There was no significant difference in the initial values of flow index, hysteresis loop or minimum apparent viscosity. The simple emulsion and the one stabilized with hydroxyethylcellulose showed decreased viscosity by the 21st day and with higher temperature, but no significant changes concerning the presence of SOD. Although there were no significant changes concerning storage time or temperature, the formulation stabilized with hydroxyethylcellulose showed a marked loss of SOD activity. The addition of SOD to the formulations studied did not affect their physical stability. Simple emulsions or emulsions stabilized with carboxypolymethylene seem to be better bases for enzyme addition than emulsion stabilized with hydroxyethylcellulose.

  14. Enhanced Ungual Permeation of Terbinafine HCl Delivered Through Liposome-Loaded Nail Lacquer Formulation Optimized by QbD Approach.

    Science.gov (United States)

    Shah, Viral H; Jobanputra, Amee

    2018-01-01

    The present investigation focused on developing, optimizing, and evaluating a novel liposome-loaded nail lacquer formulation for increasing the transungual permeation flux of terbinafine HCl for efficient treatment of onychomycosis. A three-factor, three-level, Box-Behnken design was employed for optimizing process and formulation parameters of liposomal formulation. Liposomes were formulated by thin film hydration technique followed by sonication. Drug to lipid ratio, sonication amplitude, and sonication time were screened as independent variables while particle size, PDI, entrapment efficiency, and zeta potential were selected as quality attributes for liposomal formulation. Multiple regression analysis was employed to construct a second-order quadratic polynomial equation and contour plots. Design space (overlay plot) was generated to optimize a liposomal system, with software-suggested levels of independent variables that could be transformed to desired responses. The optimized liposome formulation was characterized and dispersed in nail lacquer which was further evaluated for different parameters. Results depicted that the optimized terbinafine HCl-loaded liposome formulation exhibited particle size of 182 nm, PDI of 0.175, zeta potential of -26.8 mV, and entrapment efficiency of 80%. Transungual permeability flux of terbinafine HCl through liposome-dispersed nail lacquer formulation was observed to be significantly higher in comparison to nail lacquer with a permeation enhancer. The developed formulation was also observed to be as efficient as pure drug dispersion in its antifungal activity. Thus, it was concluded that the developed formulation can serve as an efficient tool for enhancing the permeability of terbinafine HCl across human nail plate thereby improving its therapeutic efficiency.

  15. Revisiting diesel fuel formulation from Petroleum light and middle refinery streams based on optimized engine behavior

    OpenAIRE

    Ben Amara , Arij; Dauphin , Roland; Babiker , Hassan; Viollet , Yoann; Chang , Junseok; Jeuland , Nicolas; Amer , Amer

    2016-01-01

    International audience; The share of diesel fuel in European transport sector, which currently represents over 50% of total 11 demand, is increasing, requiring massive imports of this product, while at the same time, gasoline fuels are 12 today in surplus. In terms of air pollutant emissions, gasoline and kerosene streams have shown potential 13 in achieving lower emissions in Compression Ignition (CI) engines, particularly nitrogen oxides (NOx) 14 and particulates. A new fuel formulation app...

  16. Nebulization of the acidified sodium nitrite formulation attenuates acute hypoxic pulmonary vasoconstriction

    Directory of Open Access Journals (Sweden)

    Surber Mark W

    2010-06-01

    Full Text Available Abstract Background Generalized hypoxic pulmonary vasoconstriction (HPV occurring during exposure to hypoxia is a detrimental process resulting in an increase in lung vascular resistance. Nebulization of sodium nitrite has been shown to inhibit HPV. The aim of this project was to investigate and compare the effects of nebulization of nitrite and different formulations of acidified sodium nitrite on acute HPV. Methods Ex vivo isolated rabbit lungs perfused with erythrocytes in Krebs-Henseleit buffer (adjusted to 10% hematocrit and in vivo anesthetized catheterized rabbits were challenged with periods of hypoxic ventilation alternating with periods of normoxic ventilation. After baseline hypoxic challenges, vehicle, sodium nitrite or acidified sodium nitrite was delivered via nebulization. In the ex vivo model, pulmonary arterial pressure and nitric oxide concentrations in exhaled gas were monitored. Nitrite and nitrite/nitrate were measured in samples of perfusion buffer. Pulmonary arterial pressure, systemic arterial pressure, cardiac output and blood gases were monitored in the in vivo model. Results In the ex vivo model, nitrite nebulization attenuated HPV and increased nitric oxide concentrations in exhaled gas and nitrite concentrations in the perfusate. The acidified forms of sodium nitrite induced higher levels of nitric oxide in exhaled gas and had longer vasodilating effects compared to nitrite alone. All nitrite formulations increased concentrations of circulating nitrite to the same degree. In the in vivo model, inhaled nitrite inhibited HPV, while pulmonary arterial pressure, cardiac output and blood gases were not affected. All nitrite formulations had similar potency to inhibit HPV. The tested concentration of appeared tolerable. Conclusion Nitrite alone and in acidified forms effectively and similarly attenuates HPV. However, acidified nitrite formulations induce a more pronounced increase in nitric oxide exhalation.

  17. Association of Oxidative Stress with Psychiatric Disorders.

    Science.gov (United States)

    Hassan, Waseem; Noreen, Hamsa; Castro-Gomes, Vitor; Mohammadzai, Imdadullah; da Rocha, Joao Batista Teixeira; Landeira-Fernandez, J

    2016-01-01

    When concentrations of both reactive oxygen species and reactive nitrogen species exceed the antioxidative capability of an organism, the cells undergo oxidative impairment. Impairments in membrane integrity and lipid and protein oxidation, protein mutilation, DNA damage, and neuronal dysfunction are some of the fundamental consequences of oxidative stress. The purpose of this work was to review the associations between oxidative stress and psychological disorders. The search terms were the following: "oxidative stress and affective disorders," "free radicals and neurodegenerative disorders," "oxidative stress and psychological disorders," "oxidative stress, free radicals, and psychiatric disorders," and "association of oxidative stress." These search terms were used in conjunction with each of the diagnostic categories of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders and World Health Organization's International Statistical Classification of Diseases and Related Health Problems. Genetic, pharmacological, biochemical, and preclinical therapeutic studies, case reports, and clinical trials were selected to explore the molecular aspects of psychological disorders that are associated with oxidative stress. We identified a broad spectrum of 83 degenerative syndromes and psychiatric disorders that were associated with oxidative stress. The multi-dimensional information identified herein supports the role of oxidative stress in various psychiatric disorders. We discuss the results from the perspective of developing novel therapeutic interventions.

  18. 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.

  19. RNAi Therapeutics in Autoimmune Disease

    Directory of Open Access Journals (Sweden)

    Seunghee Cha

    2013-03-01

    Full Text Available Since the discovery of RNA interference (RNAi, excitement has grown over its potential therapeutic uses. Targeting RNAi pathways provides a powerful tool to change biological processes post-transcriptionally in various health conditions such as cancer or autoimmune diseases. Optimum design of shRNA, siRNA, and miRNA enhances stability and specificity of RNAi-based approaches whereas it has to reduce or prevent undesirable immune responses or off-target effects. Recent advances in understanding pathogenesis of autoimmune diseases have allowed application of these tools in vitro as well as in vivo with some degree of success. Further research on the design and delivery of effectors of RNAi pathway and underlying molecular basis of RNAi would warrant practical use of RNAi-based therapeutics in human applications. This review will focus on the approaches used for current therapeutics and their applications in autoimmune diseases, including rheumatoid arthritis and Sjögren’s syndrome.

  20. Conflicts in the therapeutic field

    Directory of Open Access Journals (Sweden)

    Antonino Aprea

    2012-06-01

    Full Text Available How the analytical knowledge that compare human consciousness with that, even more disturbing, moving behind his fifth can be said to be “for peace”? It can be - and this will be the contribution of the proposal - the same tortuous and enigmatic of therapeutic practice, with its hesitations and his impulses, to outline a path crossing and overcoming the conflict? May, finally, peace, in the sense of feasibility of intra-and interpersonal dialectic instead of tearing and hostileconfrontation with oneself and with the other, to be a reference in some crucial pivot of ethical therapeutic work? To these questions the intervention seeks to answer retracing some of the highlights of almost three years of therapeutic work with a young woman and her family.

  1. Occurrence of hypermutable Pseudomonas aeruginosa in cystic fibrosis patients is associated with the oxidative stress caused by chronic lung inflammation

    DEFF Research Database (Denmark)

    Ciofu, Oana; Riis, Bente; Pressler, Tacjana

    2005-01-01

    Oxidative stress caused by chronic lung inflammation in patients with cystic fibrosis (CF) and chronic lung infection with Pseudomonas aeruginosa is characterized by the reactive oxygen species (ROS) liberated by polymorphonuclear leukocytes (PMNs). We formulated the hypothesis that oxidation...

  2. Reactor-produced therapeutic radioisotopes

    International Nuclear Information System (INIS)

    Knapp, F.F. Jr.

    2002-01-01

    The significant worldwide increase in therapeutic radioisotope applications in nuclear medicine, oncology and interventional cardiology requires the dependable production of sufficient levels of radioisotopes for these applications (Reba, 2000; J. Nucl. Med., 1998; Nuclear News, 1999; Adelstein and Manning, 1994). The issues associated with both accelerator- and reactor-production of therapeutic radioisotopes is important. Clinical applications of therapeutic radioisotopes include the use of both sealed sources and unsealed radiopharmaceutical sources. Targeted radiopharmaceutical agents include those for cancer therapy and palliation of bone pain from metastatic disease, ablation of bone marrow prior to stem cell transplantation, treatment modalities for mono and oligo- and polyarthritis, for cancer therapy (including brachytherapy) and for the inhibition of the hyperplastic response following coronary angioplasty and other interventional procedures (For example, see Volkert and Hoffman, 1999). Sealed sources involve the use of radiolabeled devices for cancer therapy (brachytherapy) and also for the inhibition of the hyperplasia which is often encountered after angioplasty, especially with the exponential increase in the use of coronary stents and stents for the peripheral vasculature and other anatomical applications. Since neutron-rich radioisotopes often decay by beta decay or decay to beta-emitting daughter radioisotopes which serve as the basis for radionuclide generator systems, reactors are expected to play an increasingly important role for the production of a large variety of therapeutic radioisotopes required for these and other developing therapeutic applications. Because of the importance of the availability of reactor-produced radioisotopes for these applications, an understanding of the contribution of neutron spectra for radioisotope production and determination of those cross sections which have not yet been established is important. This

  3. Preparation and characteristics of lipid nanoemulsion formulations loaded with doxorubicin

    Directory of Open Access Journals (Sweden)

    Jiang SP

    2013-08-01

    . Analysis results of in-vitro and in-vivo antitumor activities reveal that doxorubicin-loaded LNE exerts a therapeutic effect similar to that of the commercial Adriamycin. Moreover, the toxicity of doxorubicin, particularly its cardiac toxicity, is reduced. Conclusion: The present LNE formulation of doxorubicin can effectively suppress tumor growth and improve the safety of Adriamycin. Keywords: PEGylation, stability, antitumor activity

  4. [Therapeutic touch and anorexia nervosa].

    Science.gov (United States)

    Satori, Nadine

    2016-01-01

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

  5. Local normal vector field formulation for periodic scattering problems formulated in the spectral domain

    NARCIS (Netherlands)

    van Beurden, M.C.; Setija, Irwan

    2017-01-01

    We present two adapted formulations, one tailored to isotropic media and one for general anisotropic media, of the normal vector field framework previously introduced to improve convergence near arbitrarily shaped material interfaces in spectral simulation methods for periodic scattering geometries.

  6. Formulation of Pine Tar Antidandruff Shampoo Assessment and Comparison With Some Commercial Formulations

    Directory of Open Access Journals (Sweden)

    M. Gharavi

    1990-07-01

    Full Text Available In this study a pine tar shampoo as a new antidandruff formulation is presented. Assessment of antidandruff preparations has been hampered by the lack of standardized schedules, and reliable methods of evaluation.Some antidandruff agents such as : Zinc pyri-thione pine tar, selenium sulphide and (sulfure were used in shampoos. Samples were coded as numbers 1,2 formulated by us and 3,4 formulated commercially. The grading scheme based on 10 point scale, and corneocyte count was carried out on 50 selected volunte¬ers. Corneocyte count and fungal study proved that pine tor shampoo is effective against pityrosporum ovale. Draize lest was used for determination of the irritancy potential of the samples. Results showed that samples numbered 1,2 were relatively innocous in comparison with the others. I urthermore,s kin sensitination test on rabbit also confirmed the results obtained by Draize test. Consumer judgments proved that all formulations were acceptable.

  7. Design and formulation of nano-sized spray dried efavirenz. Part I: Influence of formulation parameters

    CSIR Research Space (South Africa)

    Katata, L

    2012-10-01

    Full Text Available statistical design with an L8 orthogonal array, was implemented to optimise the formulation parameters of PCL-EFV nanoparticles. The types of sugar (lactose or trehalose), surfactant concentration and solvent (dichloromethane and ethyl acetate) were chosen...

  8. 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

  9. Intracerebral Hemorrhage, Oxidative Stress, and Antioxidant Therapy

    Directory of Open Access Journals (Sweden)

    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.

  10. Consistency of canonical formulation of Horava gravity

    International Nuclear Information System (INIS)

    Soo, Chopin

    2011-01-01

    Both the non-projectable and projectable version of Horava gravity face serious challenges. In the non-projectable version, the constraint algebra is seemingly inconsistent. The projectable version lacks a local Hamiltonian constraint, thus allowing for an extra graviton mode which can be problematic. A new formulation (based on arXiv:1007.1563) of Horava gravity which is naturally realized as a representation of the master constraint algebra (instead of the Dirac algebra) studied by loop quantum gravity researchers is presented. This formulation yields a consistent canonical theory with first class constraints; and captures the essence of Horava gravity in retaining only spatial diffeomorphisms as the physically relevant non-trivial gauge symmetry. At the same time the local Hamiltonian constraint is equivalently enforced by the master constraint.

  11. Formulation of diclofenac for dermal delivery.

    Science.gov (United States)

    Goh, Choon Fu; Lane, Majella E

    2014-10-01

    Diclofenac (DF) was first synthesized in the 1960's and is currently available as ophthalmic, oral, parenteral, rectal and skin preparations. This review focuses on the administration of DF to the skin. As a member of the non-steroidal anti-inflammatory (NSAID) group of drugs the primary indications of DF are for the management of inflammation and pain but it is also used to treat actinic keratosis. The specific aims of this paper are to: (i) provide an overview of the pharmacokinetics and metabolism of DF following oral and topical administration; (ii) examine critically the various formulation approaches which have been investigated to enhance dermal delivery of DF; and (iii) identify new formulation strategies for enhanced DF skin penetration. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Consistency of canonical formulation of Horava gravity

    Energy Technology Data Exchange (ETDEWEB)

    Soo, Chopin, E-mail: cpsoo@mail.ncku.edu.tw [Department of Physics, National Cheng Kung University, Tainan, Taiwan (China)

    2011-09-22

    Both the non-projectable and projectable version of Horava gravity face serious challenges. In the non-projectable version, the constraint algebra is seemingly inconsistent. The projectable version lacks a local Hamiltonian constraint, thus allowing for an extra graviton mode which can be problematic. A new formulation (based on arXiv:1007.1563) of Horava gravity which is naturally realized as a representation of the master constraint algebra (instead of the Dirac algebra) studied by loop quantum gravity researchers is presented. This formulation yields a consistent canonical theory with first class constraints; and captures the essence of Horava gravity in retaining only spatial diffeomorphisms as the physically relevant non-trivial gauge symmetry. At the same time the local Hamiltonian constraint is equivalently enforced by the master constraint.

  13. Principles of ration formulation for ruminants

    International Nuclear Information System (INIS)

    Jayasuriya, M.C.N.

    2002-01-01

    Feeding standards as practiced in developed countries could be misleading when non-conventional feed resources are used in formulating rations for ruminant livestock in developing countries. They tend to reject the poor quality feeds that are available in vast quantities. The non-availability of good quality forage throughout the year and the need to optimise the efficiency of utilisation of locally available feed resources have lead to the application of basic nutritional principles when considering ration formulation. The alternative approach to the use of feeding standards would be to ensure that the production system matches the available resources. The development of feed supplementation strategies based on locally available feed resources require the understanding of the relative roles and nutrient needs of the two-compartment system represented by the micro-organisms in the rumen and the host animal. (author)

  14. Spray drying formulation of amorphous solid dispersions.

    Science.gov (United States)

    Singh, Abhishek; Van den Mooter, Guy

    2016-05-01

    Spray drying is a well-established manufacturing technique which can be used to formulate amorphous solid dispersions (ASDs) which is an effective strategy to deliver poorly water soluble drugs (PWSDs). However, the inherently complex nature of the spray drying process coupled with specific characteristics of ASDs makes it an interesting area to explore. Numerous diverse factors interact in an inter-dependent manner to determine the final product properties. This review discusses the basic background of ASDs, various formulation and process variables influencing the critical quality attributes (CQAs) of the ASDs and aspects of downstream processing. Also various aspects of spray drying such as instrumentation, thermodynamics, drying kinetics, particle formation process and scale-up challenges are included. Recent advances in the spray-based drying techniques are mentioned along with some future avenues where major research thrust is needed. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Canonical formulation of general-relativistic theories

    International Nuclear Information System (INIS)

    Bergmann, P.G.

    1987-01-01

    With the birth of quantum field theory in the late twenties physicists decided that nature could not be half classical and half quantum, and that the gravitational field ought to be quanticized, just as the electromagnetic field had been. One could accept the group of differomorphisms as a fundamental characteristic of general relativity (and indeed of all general-relativistic theories), and proceed to construct a quantum field-theory that was adapted to that group. Quantization would be attempted by way of a Hamiltonian formulation of the (classical) theory, and quantum commutation relations be patterned after the Poisson brackets arising in that formulation. This program is usually called the canonical quantization program, whereas the weak-field approach is known as covariant quantization. The first steps, conceived entirely within the framework of the classical theory, turned out to be beset with technical and conceptual difficulties, which today are essentially resolved. In this paper the author traces out these initial steps

  16. Planar multibody dynamics formulation, programming and applications

    CERN Document Server

    Nikravesh, Parviz E

    2007-01-01

    Introduction Multibody Mechanical Systems Types of Analyses Methods of Formulation Computer Programming Application Examples Unit System Remarks Preliminaries Reference Axes Scalars and Vectors Matrices Vector, Array, and Matrix Differentiation Equations and Expressions Remarks Problems Fundamentals of Kinematics A Particle Kinematics of a Rigid Body Definitions Remarks Problems Fundamentals of Dynamics Newton's Laws of Motion Dynamics of a Body Force Elements Applied Forces Reaction Force Remarks Problems Point-Coordinates: Kinematics Multipoint

  17. Alternative formulations of the electricity tax

    International Nuclear Information System (INIS)

    2003-01-01

    According to EFTA's surveillance authority ESA, the current form of the electricity tax may have a competition distorting effect since only the industry and a few other sectors are exempt from it. This document discusses four alternative formulations of the electricity tax: same tax for all business sectors and households, defining a maximum payment for each firm, introduce a tax on power transmission, or have taxation only on power used for heating.

  18. Formulation and Evaluation of Bioadhesive Cyproheptadine Tablets ...

    African Journals Online (AJOL)

    Results: The shear stress of 3 % solution of HPMC was greater than that of an equivalent concentration of Carbopol 934P. The values of K, n, R2 and detachment force for the optimized formulation (F0) were 0.269, 0.696, 0.964 and 0.066 Newton (N), respectively, and showed good correlation with the predicted values, thus ...

  19. Ising formulations of many NP problems

    OpenAIRE

    Lucas, Andrew

    2013-01-01

    We provide Ising formulations for many NP-complete and NP-hard problems, including all of Karp's 21 NP-complete problems. This collects and extends mappings to the Ising model from partitioning, covering and satisfiability. In each case, the required number of spins is at most cubic in the size of the problem. This work may be useful in designing adiabatic quantum optimization algorithms.

  20. Ising formulations of many NP problems

    Directory of Open Access Journals (Sweden)

    Andrew eLucas

    2014-02-01

    Full Text Available We provide Ising formulations for many NP-complete and NP-hard problems, including all of Karp's 21 NP-complete problems. This collects and extends mappings to the Ising model from partitioning, covering and satisfiability. In each case, the required number of spins is at most cubic in the size of the problem. This work may be useful in designing adiabatic quantum optimization algorithms.

  1. Microcanonical ensemble formulation of lattice gauge theory

    International Nuclear Information System (INIS)

    Callaway, D.J.E.; Rahman, A.

    1982-01-01

    A new formulation of lattice gauge theory without explicit path integrals or sums is obtained by using the microcanonical ensemble of statistical mechanics. Expectation values in the new formalism are calculated by solving a large set of coupled, nonlinear, ordinary differential equations. The average plaquette for compact electrodynamics calculated in this fashion agrees with standard Monte Carlo results. Possible advantages of the microcanonical method in applications to fermionic systems are discussed

  2. Path Integral Formulation of Anomalous Diffusion Processes

    OpenAIRE

    Friedrich, Rudolf; Eule, Stephan

    2011-01-01

    We present the path integral formulation of a broad class of generalized diffusion processes. Employing the path integral we derive exact expressions for the path probability densities and joint probability distributions for the class of processes under consideration. We show that Continuous Time Random Walks (CTRWs) are included in our framework. A closed expression for the path probability distribution of CTRWs is found in terms of their waiting time distribution as the solution of a Dyson ...

  3. FORMULATION AND EVALUATION OF A HERBAL SHAMPOO

    OpenAIRE

    Gouri Kumar Dash* and Noor Husna Nazirah Binti A. Razak

    2017-01-01

    The study was aimed at formulating and evaluating a complete herbal shampoo containing only traditionally used plant materials. The shampoo contained extracts of Hibiscus rosa-sinensis, Azadirachta indica, Trigonella foenumgraecum, Phyllanthus emblica, Sapindus mukorossi, Acacia concinna and fresh juice of Aloe vera. The physicochemical parameters such as colour, clarity, pH, skin irritation, percentage of solid contents, dirt dispersion, foaming ability and foam stability, wetting time and c...

  4. Prednisone raw material characterization and formulation development

    OpenAIRE

    Leonardo Henrique Toehwé; Livia Deris Prado; Helvécio Vinícius Antunes Rocha

    2018-01-01

    ABSTRACT Solid dosage forms for oral use, particularly tablets, are the most highly used dosage forms in therapy because they are easily administered, have high productivity and relatively low cost and provide a more stable drug to form a semi-solid net. Numerous parameters influence the quality of the final dosage form. In this study, the dissolution profile of 20-mg prednisone tablets bioequivalent to the reference product and three test formulations were evaluated using stability testing. ...

  5. Therapy Talk: Analyzing Therapeutic Discourse

    Science.gov (United States)

    Leahy, Margaret M.

    2004-01-01

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

  6. Therapeutic approaches to genetic disorders

    African Journals Online (AJOL)

    salah

    Although prevention is the ideal goal for genetic disorders, various types of therapeutic ... The patient being ... pirical or aimed at controlling or mediating signs and symptoms without care. ... plications and gene therapy approaches .... genes family, have opened a wide and .... cancer where nanoparticles are used to.

  7. Medical therapeutic effect of hyperthyroidism

    International Nuclear Information System (INIS)

    Lee, K.B.

    1980-01-01

    In order to compare the therapeutic effect as well as side effects between antithyroid therapy and radioiodine therapy in hyperthyroidism, the author evaluated 111 cases of hyperthyroidism which were composed of 57 patients with antithyroid treatment, 23 patients with combined treatment comprising of antithyroid and radioactive iodine ( 131 I) and 31 patients with treatment of 131 I alone. (author)

  8. Application of single-vial ready-for-use formulation of 111In- or 177Lu-labelled somatostatin analogs.

    Science.gov (United States)

    de Blois, Erik; Chan, Ho Sze; de Zanger, Rory; Konijnenberg, Mark; Breeman, Wouter A P

    2014-02-01

    For the sake of safety it would be desirable to store and transport the ready-for-use liquid formulation (diagnostics and therapeutics) of radiolabelled peptides. The use of ethanol, in combination with a mixture of gentisic- and ascorbic acid, has superior effects on stabilizing radiolabelled somatostatin analogs. As a consequence, (111)In- and (177)Lu-labelled somatostatin analogs can be stored and transported in a single-vial ready-for-use liquid formulation up to 7 days after radiolabelling. © 2013 Published by Elsevier Ltd.

  9. Trigger chemistries for better industrial formulations.

    Science.gov (United States)

    Wang, Hsuan-Chin; Zhang, Yanfeng; Possanza, Catherine M; Zimmerman, Steven C; Cheng, Jianjun; Moore, Jeffrey S; Harris, Keith; Katz, Joshua S

    2015-04-01

    In recent years, innovations and consumer demands have led to increasingly complex liquid formulations. These growing complexities have provided industrial players and their customers access to new markets through product differentiation, improved performance, and compatibility/stability with other products. One strategy for enabling more complex formulations is the use of active encapsulation. When encapsulation is employed, strategies are required to effect the release of the active at the desired location and time of action. One particular route that has received significant academic research effort is the employment of triggers to induce active release upon a specific stimulus, though little has translated for industrial use to date. To address emerging industrial formulation needs, in this review, we discuss areas of trigger release chemistries and their applications specifically as relevant to industrial use. We focus the discussion on the use of heat, light, shear, and pH triggers as applied in several model polymeric systems for inducing active release. The goal is that through this review trends will emerge for how technologies can be better developed to maximize their value through industrial adaptation.

  10. What is Quantum Mechanics? A Minimal Formulation

    Science.gov (United States)

    Friedberg, R.; Hohenberg, P. C.

    2018-03-01

    This paper presents a minimal formulation of nonrelativistic quantum mechanics, by which is meant a formulation which describes the theory in a succinct, self-contained, clear, unambiguous and of course correct manner. The bulk of the presentation is the so-called "microscopic theory", applicable to any closed system S of arbitrary size N, using concepts referring to S alone, without resort to external apparatus or external agents. An example of a similar minimal microscopic theory is the standard formulation of classical mechanics, which serves as the template for a minimal quantum theory. The only substantive assumption required is the replacement of the classical Euclidean phase space by Hilbert space in the quantum case, with the attendant all-important phenomenon of quantum incompatibility. Two fundamental theorems of Hilbert space, the Kochen-Specker-Bell theorem and Gleason's theorem, then lead inevitably to the well-known Born probability rule. For both classical and quantum mechanics, questions of physical implementation and experimental verification of the predictions of the theories are the domain of the macroscopic theory, which is argued to be a special case or application of the more general microscopic theory.

  11. Development of formulation device for periodontal disease.

    Science.gov (United States)

    Sato, Yasuhiko; Oba, Takuma; Watanabe, Norio; Danjo, Kazumi

    2012-01-01

    In addition to providing standard surgical treatment that removes the plaque and infected tissues, medications that can regenerate periodontal tissue are also required in the treatment of periodontal disease. As a form of regenerative medication, various growth factors are expected to be used while treating periodontal disease. A protein-like growth factor is often developed as a lyophilized product with dissolution liquid, considering its instability in the solution state. We have clarified that the formulation for periodontal disease needs to be viscous. When the lyophilized product was dissolved using a sticky solution, various problems were encountered, difficulty in dissolving and air bubbles, for example, and some efforts were needed to prepare the formulation. In this research, to identify the problem of preparing a viscous formulation, a lyophilized product (placebo) and sticky liquid were prepared by using vial and ampoule as the conventional containers. Based on these problems, a prototype administration device was developed, and its functionality was confirmed. As a result, it was suggested that the device with a useful mixing system that could shorten the preparation time was developed.

  12. Oxide ceramics

    International Nuclear Information System (INIS)

    Ryshkewitch, E.; Richerson, D.W.

    1985-01-01

    The book explores single-phase ceramic oxide systems from the standpoint of physical chemistry and technology. This second edition also focuses on advances in technology since publication of the original edition. These include improvements in raw materials and forming and sintering techniques, and the major role that oxide ceramics have had in development of advanced products and processes. The text is divided into five major sections: general fundamentals of oxide ceramics, advances in aluminum oxide technology, advances in zirconia technology, and advances in beryllium oxide technology

  13. Formulation of humic-based soil conditioners

    Science.gov (United States)

    Amanova, M. A.; Mamytova, G. A.; Mamytova, B. A.; Kydralieva, K. A.; Jorobekova, Sh. J.

    2009-04-01

    The goal of the study is to prepare soil conditioners (SC) able to carry out the following functions: (i) the chemical conditioning of soil mainly comprising the adjustment of pH, (ii) the balancing of inorganic nutrients, (iii) the physical conditioning of soil mainly comprising the improvement of water permeability, air permeability and water retention properties, and (iv) improvement of the ecological system concerning of useful microorganisms activity in the soil. The SC was made of a mixture of inorganic ingredients, a chemical composition and physical and chemical properties of which promoted improvement of physical characteristic of soil and enrichment by its mineral nutritious elements. In addition to aforesaid ingredients, this soil conditioner contains agronomical-valued groups of microorganisms having the function promoting the growth of the crop. As organic component of SC humic acids (HA) was used. HA serve many major functions that result in better soil and plant health. In soil, HA can increase microbial and mycorrhizal activity while enhancing nutrient uptake by plant roots. HA work as a catalyst by stimulating root and plant growth, it may enhance enzymatic activity that in turn accelerates cell division which can lead to increased yields. HA can help to increase crop yields, seed germination, and much more. In short, humic acids helps keep healthy plants health. The first stage goal was to evaluate mineral and organic ingredients for formulation of SC. Soil conditioners assessed included ash and slag. The use of slags has been largelly used in agriculture as a source of lime and phosphoric acid. The silicic acid of slags reduces Al-acitivity thus, promoting a better assimilation of P-fertilizer by plants. Additionally, silicic acid is also known to improve soil moisture capacity, thus enhancing soil water availability to plants. Physico-chemical characteristics of ash and slag were determined, as a total - about 20 samples. Results include

  14. New waste based clinkers: Belite and lime formulations

    International Nuclear Information System (INIS)

    Raupp-Pereira, Fabiano; Ball, Richard James; Rocha, Joao; Labrincha, Joao A.; Allen, Geoffrey C.

    2008-01-01

    This work describes the formulation of new belite-based (CR2) and lime-based (CR3) cementitious materials derived from industrial wastes, such as sludges (generated in the Al-anodising and surface coating industrial processes, potable water filtration/cleaning operations and in marble sawing processes) and foundry sand. Powder mixtures were prepared and fired at different temperatures. For comparison, similar formulations were prepared with pre-treated and commercially available natural raw materials and processed in similar conditions. The thermal process was followed by differential scanning calorimetry (DSC) and high-temperature powder X-ray diffraction (HT-XRD) studies. The CR2 clinker was found to contain belite as the main cementitious phase, the main polymorph being identified by NMR. The CR3 clinker contained common cementitious phases, such as C 3 A and C 3 S, but free lime and calcium aluminium oxide sulphates were also identified by high temperature XRD and NMR. Then the corresponding cement was prepared and the evolution of the mechanical strength with time was evaluated. The lime-based cement obtained from wastes shows a stronger hardening character than the standard material, which tends to show dusting phenomena due to the presence of a reasonable amount of free lime (as the result of its expansive reaction with ambient moisture). Some fluxing impurities (e.g. alkalis) present in the waste materials improve the overall reactivity of the mixture and induces the combination of the lime in CR3. Raman, XPS and FIB techniques were used to fully characterise the aged cements

  15. Aptamer therapeutics: A review of current practice

    International Nuclear Information System (INIS)

    Perkins, A.C.; Missailidis, S.

    2007-01-01

    Full text: The development of nuclease resistant oligonucleotide agents known as aptamers, offers an alternative to antibodies as targeting, diagnostic and delivery agents. The production technique of specific receptor binding molecules based on defined nucleic acid sequences is known as systematic evolution of ligands by exponential enrichment (SELEX). Using this technique, aptamers can be produced rapidly and with high homogeneity. Furthermore, they are stable over long term storage at ambient room temperatures. A monomeric aptamer is small in size, with a molecular weight as low as 5 to 10 kDa. However, the aptamer molecule may be used as a building block for custom designed targeting agents, offering several advantages. Aptamers have been found to bind their targets with high specificity and with dissociation constants in the subnanomolar or picomolar range. The first pharmaceutical aptamer formulation, Macugen (pegaptanib sodium injection) was approved in the United States in December of 2004. This is an anti-VEGF aptamer formulation used for the treatment of Neovascular agerelated macular degeneration. Other possibilities in cardiovascular, neurodegenerative and tropical medicine are apparent. As tumour targeting agents, aptamers penetrate tissues readily, reach peak levels quickly and clear from the body rapidly, thus having properties of low toxicity and immunoreactivity. Work with radiolabelled aptamers is limited to pre-clinical studies, but the body of evidence is steadily growing and aptamers are emerging as valuable clinical products for diagnostic imaging and therapy. Peptide coupling reactions between amino and carboxylic groups offer the possibility of labelling the aptamers with a number of chelators that, coupled with appropriate radionuclides, would generate novel targeted radiopharmaceuticals for the diagnosis and therapy of disease. The unparalleled combinatorial chemical diversity, small size and modification ability of aptamers is expected to

  16. Confirming the RNAi-mediated mechanism of action of siRNA-based cancer therapeutics in mice

    OpenAIRE

    Judge, Adam D.; Robbins, Marjorie; Tavakoli, Iran; Levi, Jasna; Hu, Lina; Fronda, Anna; Ambegia, Ellen; McClintock, Kevin; MacLachlan, Ian

    2009-01-01

    siRNAs that specifically silence the expression of cancer-related genes offer a therapeutic approach in oncology. However, it remains critical to determine the true mechanism of their therapeutic effects. Here, we describe the preclinical development of chemically modified siRNA targeting the essential cell-cycle proteins polo-like kinase 1 (PLK1) and kinesin spindle protein (KSP) in mice. siRNA formulated in stable nucleic acid lipid particles (SNALP) displayed potent antitumor efficacy in b...

  17. Anti Inflammatory and Anti Arthritic Activity of Different Milk Based Formulation of Curcumin in Rat Model.

    Science.gov (United States)

    Sumeet, Gupta; Rachna, Kumria; Samrat, Chauhan; Ipshita, Chattopadhyaya; Vikas, Jhawat; Manu, Sharma

    2018-02-14

    Inflammation is the key mediator for arthritis. Plant based products are most useful for treating various disorders, but at the same time drug absorption is utmost important for effective therapy. The present aim of our study was to find out the therapeutic concern in pharmacokinetic and pharmacodynamic parameters in an arthritis induced rat model. Carregenan and complete Freud's adjuvant, both were used for an arthritis induction as an animal model. Formulation of curcumin was prepared in different quality of milk brand, high fat milk with ghee and in an aqueous suspension. They were administered orally to the rats for 21 days continuously. Different pharmacodyanmic parameters were analyzed which include percentage inhibition of inflammation, cytokines (IL-6 and TNF-α), hematological levels, X-Rays and histology condition. Pharmacokinetics was also determined like Cmax, Tmax and Kel using HPLC method. The result concludes that, curcumin in full fat milk with ghee and full fat curcumin formulation treated group showed a higher statistical significant effect in the prevention of inflammation in both the models. The presence of curcumin in plasma was higher only in full fat with ghee formulation and full fat milk formulation treated group when compared to the other groups. Hence, it concludes that the presence of adjuvant act as an enhancer can increase the bioavailability of curcumin for achieving maximum effectiveness. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Biominetic High Density Lipoproteins for the Delivery of Therapeutic Oligonucleotides

    Science.gov (United States)

    Tripathy, Sushant

    Advances in nanotechnology have brought about novel inorganic and hybrid nanoparticles with unique physico-chemical properties that make them suitable for a broad range of applications---from nano-circuitry to drug delivery. A significant part of those advancements have led to ground-breaking discoveries that have changed the approaches to formulation of therapeutics against diseases, such as cancer. Now-a-days the focus does not lie solely on finding a candidate small-molecule therapeutic with minimal adverse effects, but researchers are looking up to nanoparticles to improve biodistribution and biocompatibility profile of clinically proven therapeutics. The plethora of conjugation chemistries offered by currently extant inorganic nanoparticles have, in recent years, led to great leaps in the field of biomimicry---a modality that promises high biocompatibility. Further, in the pursuit of highly specific therapeutic molecules, researchers have turned to silencing oligonucleotides and some have already brought together the strengths of nanoparticles and silencing oligonucleotides in search of an efficacious therapy for cancer with minimal adverse effects. This dissertation work focuses on such a biomimetic platform---a gold nanoparticle based high density lipoprotein biomimetic (HDL NP), for the delivery of therapeutic oligonucleotides. The first chapter of this body of work introduces the molecular target of the silencing oligonucleotides---VEGFR2, and its role in the progression of solid tumor cancers. The background information also covers important aspects of natural high density lipoproteins (HDL), especially their innate capacity to bind and deliver exogenous and endogenous silencing oligonucleotides to tissues that express their high affinity receptor SRB1. We subsequently describe the synthesis of the biomimetic HDL NP and its oligonucleotide conjugates, and establish their biocompatibility. Further on, experimental data demonstrate the efficacy of silencing

  19. The state-of-play and future of antibody therapeutics.

    Science.gov (United States)

    Elgundi, Zehra; Reslan, Mouhamad; Cruz, Esteban; Sifniotis, Vicki; Kayser, Veysel

    2017-12-01

    It has been over four decades since the development of monoclonal antibodies (mAbs) using a hybridoma cell line was first reported. Since then more than thirty therapeutic antibodies have been marketed, mostly as oncology, autoimmune and inflammatory therapeutics. While antibodies are very efficient, their cost-effectiveness has always been discussed owing to their high costs, accumulating to more than one billion dollars from preclinical development through to market approval. Because of this, therapeutic antibodies are inaccessible to some patients in both developed and developing countries. The growing interest in biosimilar antibodies as affordable versions of therapeutic antibodies may provide alternative treatment options as well potentially decreasing costs. As certain markets begin to capitalize on this opportunity, regulatory authorities continue to refine the requirements for demonstrating quality, efficacy and safety of biosimilar compared to originator products. In addition to biosimilars, innovations in antibody engineering are providing the opportunity to design biobetter antibodies with improved properties to maximize efficacy. Enhancing effector function, antibody drug conjugates (ADC) or targeting multiple disease pathways via multi-specific antibodies are being explored. The manufacturing process of antibodies is also moving forward with advancements relating to host cell production and purification processes. Studies into the physical and chemical degradation pathways of antibodies are contributing to the design of more stable proteins guided by computational tools. Moreover, the delivery and pharmacokinetics of antibody-based therapeutics are improving as optimized formulations are pursued through the implementation of recent innovations in the field. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Herbal infusions of black seed and wheat germ oil: Their chemical profiles, in vitro bio-investigations and effective formulations as Phyto-Nanoemulsions.

    Science.gov (United States)

    Gumus, Z Pinar; Guler, Emine; Demir, Bilal; Barlas, F Baris; Yavuz, Murat; Colpankan, Dilara; Senisik, A Murat; Teksoz, Serap; Unak, Perihan; Coskunol, Hakan; Timur, Suna

    2015-09-01

    The reported studies related to black seed oil (BSO) and wheat germ oil (WGO) have illustrated that they have a wide range of biological activities. Therefore, enhancing the amount of bio-active compounds that caused higher cell based anti-oxidative effect as well as cell proliferation, etc. in seed oils, infusion of crude plant material has been gained importance as a traditional technique. Herein, we accomplished the infusion of Calendula flowers that also contains many phyto-constituents into BSO and WGO. After the infusion of oils, the change of phytochemical amount was investigated and evaluated according to the oils by chromatography, radical scavenging activity. Subsequently, for investigating the biological impact upon live cells, cytotoxicity, cell-based antioxidant capacity, wound healing and radioprotective activity were tested with monkey kidney fibroblast like cells (Vero) and HaCaT keratinocytes. In vitro cell based experiments (wound healing and radioprotective activity) confirmed that Calendula infused BSO and WGO have greater bio-activity when compared to those plain forms. The herbal oils prepared with an effective extraction technique were incorporated into nanoemulsion systems which will be then called as 'Phyto-Nanoemulsion'. After herbal oil biomolecules were encapsulated into nanoemulsion based delivery systems, the designed formulations were investigated in terms of biological activities. In conclusion, these preparations could be a good candidate as a part of dermal cosmetic products or food supplements which have the therapeutic efficiency, especially after radio- or chemotherapy. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Herbo Mineral Formulations (Rasaoushadhies) of Ayurveda an Amazing Inheritance of Ayurvedic Pharmaceutics

    Science.gov (United States)

    Chaudhary, Anand; Singh, Neetu

    2010-01-01

    The one of the oldest system of medicine, Ayurveda is momentous in audience of worldwide on virtue of its holistic approach of life. Formulations of Ayurveda consist of substances of herbal, mineral/metal and animal origin which are processed pharmaceutical to have therapeutic effects. This is attribute of processes of Shodhan (purification/potentiation), Bhavana (impregation /levigation) and Marana (incineration/calcinations) of Rasa Shastra which acclimatize these toxic industrial matter to a effective remedies known as herbo mineral formulations (Rasaoushadhies) of Ayurveda. In recent past there is prevalence of some doubt on safety and efficacy of these medicines. In this review paper we tried to justify application of these medicines as these are time tested and showed wonderful clinical adaptability. We also attempted to establish new facts of figures of core science in explanation of these medicines. PMID:22557419

  2. Light-triggerable formulations for the intracellular controlled release of biomolecules.

    Science.gov (United States)

    Lino, Miguel M; Ferreira, Lino

    2018-05-01

    New therapies based on the use of biomolecules [e.g., proteins, peptides, and non-coding (nc)RNAs] have emerged during the past few years. Given their instability, adverse effects, and limited ability to cross cell membranes, delivery systems are required to fully reveal their biological potential. Sophisticated nanoformulations responsive to light offer an excellent opportunity for the controlled release of these biomolecules, enabling the control of timing, duration, location, and dosage. In this review, we discuss the design principles for the delivery of biomolecules, in particular proteins and RNA-based therapeutics, by light-triggerable formulations. We further discuss the opportunities offered by these formulations in terms of endosomal escape, as well as their limitations. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. Antioxidant activity of Matricaria chamomilla L. extract and clinical efficacy of cosmetic formulations containing this extract and its isolated compounds

    Directory of Open Access Journals (Sweden)

    Ananda T. Nóbrega

    2013-12-01

    Full Text Available Topical application of antioxidants has proven to be effective in protecting the skin against oxidative damage. Matricaria chamomilla L. extract has been used in cosmetic formulations. The aim of this study was to evaluate the antioxidant potential of chamomile extract as well as the clinical efficacy on skin hydration and mechanical properties of skin. The antioxidant activity of chamomile extract was evaluated by chemiluminescence (IC50 = 0.14 μg/mL. Stable formulations were supplemented with 0,5 cg/g α-bisabolol or cg/gwith 5,0 of Matricaria chamomile glycolic extract or with 0,01 cg/g of apigenin and applied on the volar forearm and face of 25 female subjects. Skin physiology was assessed before and after 2 hours (single application and after a 2- and 4-week period of daily application. After a single application, all formulations increased the stratum corneum water content but only α-bisabolol and chamomile extract formulations reduced TEWL. The formulation with chamomile extract has shown the most pronounced result in the reduction of TEWL (27%. However, after 2- and 4-week application, only the extract formulation increased stratum corneum water content compared with the vehicle. Chamomile extract was effective in neutralizing free radicals and therefore presents an interesting potential in cosmetic formulations for this purpose.

  4. Characterization of kaolin and granite waste for formulation of porcelain stoneware tiles

    International Nuclear Information System (INIS)

    Luna da Silveira, G.C.; Acchar, W.; Gomes, U.U.; Silva, B.K.O.; Luna da Silveira, R.V.; Labrincha, J.A.; Costa, M.C.P.

    2016-01-01

    To produce a stoneware tiles is necessary develop a formulation that satisfies their structural characteristics, micro-structural, physical and mechanical properties. Thus, in order to create a formulation for porcelain stoneware tiles that give use to kaolin and granite waste used in the production of ceramic materials were asked the following characterizations: chemical analysis, mineralogical, thermal and particle size. We found that in the kaolin sample it presents a rate of silicon oxide and aluminum oxide similar to those found in the work of other investigators, about 45.23% SiO2 and 37.39% Al_2O_3. In the granite waste, the percentage of silicon oxide and aluminum oxide are also similar to those observed in other studies, with about 74.89% SiO2 and 10.54% Al_2O_3. Both the percentage of SiO_2 and Al_2O_3 founded in these two samples satisfy the percentage required in the manufacturing of porcelain stoneware tiles. (author)

  5. Development of ELISA-based methods to measure the anti-malarial drug chloroquine in plasma and in pharmaceutical formulations

    DEFF Research Database (Denmark)

    Khalil, Insaf F; Alifrangis, Michael; Recke, Camilla

    2011-01-01

    In Central and South America and Eastern and Southern Africa, Plasmodium vivax infections accounts for 71-81% and 5% of malaria cases, respectively. In these areas, chloroquine (CQ) remains the treatment of choice for P. vivax malaria. In addition, CQ has recently proven to be an effective HIV-1...... therapeutic agent. There is a dire need to continue monitoring quality of CQ as there is a major influx of substandard and fake formulations into malaria-endemic countries. The use of fake/substandard drugs will result in sub-therapeutic levels endangering the patient and possibly select for parasite...

  6. Dispersible formulation of artemether/lumefantrine: specifically developed for infants and young children

    Directory of Open Access Journals (Sweden)

    Sagara Issaka

    2009-10-01

    Full Text Available Abstract Infants and children under five years of age are the most vulnerable to malaria with over 1,700 deaths per day from malaria in this group. However, until recently, there were no WHO-endorsed paediatric anti-malarial formulations available. Artemisinin-based combination therapy is the current standard of care for patients with uncomplicated falciparum malaria in Africa. Artemether/lumefantrine (AL meets WHO pre-qualification criteria for efficacy, safety and quality. Coartem®, a fixed dose combination of artemether and lumefantrine, has consistently achieved cure rates of >95% in clinical trials. However, AL tablets are inconvenient for caregivers to administer as they need to be crushed and mixed with water or food for infants and young children. Further, in common with other anti-malarials, they have a bitter taste, which may result in children spitting the medicine out and not receiving the full therapeutic dose. There was a clear unmet medical need for a formulation of AL specifically designed for children. Ahead of a call from WHO for child-friendly medicines, Novartis, working in partnership with Medicines for Malaria Venture (MMV, started the development of a new formulation of AL for infants and young children: Coartem® Dispersible. The excellent efficacy, safety and tolerability already demonstrated by AL tablets were confirmed with dispersible AL in a large trial comparing the crushed tablets with dispersible tablets in 899 African children with falciparum malaria. In the evaluable population, 28-day PCR-corrected cure rates of >96% were achieved. Further, its sweet taste means that it is palatable for children, and the dispersible formulation makes it easier for caregivers to administer than bitter crushed tablets. Easing administration may foster compliance, hence improving therapeutic outcomes in infants and young children and helping to preserve the efficacy of ACT.

  7. 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.

  8. Conversational evidence in therapeutic dialogue.

    Science.gov (United States)

    Strong, Tom; Busch, Robbie; Couture, Shari

    2008-07-01

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

  9. [Therapeutic use of cannabis derivatives].

    Science.gov (United States)

    Benyamina, Amine; Reynaud, Michel

    2014-02-01

    The therapeutic use of cannabis has generated a lot of interest in the past years, leading to a better understanding of its mechanisms of action. Countries like the United States and Canada have modified their laws in order to make cannabinoid use legal in the medical context. It's also the case in France now, where a recent decree was issued, authorizing the prescription of medication containing "therapeutic cannabis" (decree no. 2013-473, June 5, 2013). Cannabinoids such as dronabinol, Sativex and nabilone have been tested for the treatment of acute and chronic pain. These agents are most promising to relieve chronic pain associated with cancer, with human immunodeficiency virus infection and with multiple sclerosis. However, longer-term studies are required to determine potential long-term adverse effects and risks of misuse and addiction.

  10. Therapeutic Dancing for Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Lorenna Pryscia Carvalho Aguiar

    2016-06-01

    Full Text Available Therapeutic dancing has been advocated as an effective adjunct to conventional physical therapies for people living with Parkinson's disease (PD. This systematic review evaluates studies on the outcomes of different dance genres on mobility and quality of life in PD. We searched databases including CINHAL (1982–2015, Medline (1922–2015, Scopus (1996–2015, Web of Science (2002–2015, Embase (2007–2015, PEDro (1999–2015 and the Cochrane Library (1996–2015. The key words were: Parkinson's disease, Parkinson*, Parkinsonism, dance, dance therapy, dance genres, safety, feasibility, and quality of life. Two independent investigators reviewed the texts. Only randomized controlled trials, quasirandomized controlled trials, and case series studies were included. There was emerging evidence that therapeutic dance can be safe and feasible for people with mild to moderately severe PD, with beneficial effects on walking, freezing of gait, and health related quality of life.

  11. Therapeutic approaches for celiac disease

    Science.gov (United States)

    Plugis, Nicholas M.; Khosla, Chaitan

    2015-01-01

    Celiac disease is a common, lifelong autoimmune disorder for which dietary control is the only accepted form of therapy. A strict gluten-free diet is burdensome to patients and can be limited in efficacy, indicating there is an unmet need for novel therapeutic approaches to supplement or supplant dietary therapy. Many molecular events required for disease pathogenesis have been recently characterized and inspire most current and emerging drug-discovery efforts. Genome-wide association studies (GWAS) confirm the importance of human leukocyte antigen genes in our pathogenic model and identify a number of new risk loci in this complex disease. Here, we review the status of both emerging and potential therapeutic strategies in the context of disease pathophysiology. We conclude with a discussion of how genes identified during GWAS and follow-up studies that enhance susceptibility may offer insight into developing novel therapies. PMID:26060114

  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. Dry age-related macular degeneration: mechanisms, therapeutic targets, and imaging.

    Science.gov (United States)

    Bowes Rickman, Catherine; Farsiu, Sina; Toth, Cynthia A; Klingeborn, Mikael

    2013-12-13

    Age-related macular degeneration is the leading cause of irreversible visual dysfunction in individuals over 65 in Western Society. Patients with AMD are classified as having early stage disease (early AMD), in which visual function is affected, or late AMD (generally characterized as either "wet" neovascular AMD, "dry" atrophic AMD or both), in which central vision is severely compromised or lost. Until recently, there have been no therapies available to treat the disorder(s). Now, the most common wet form of late-stage AMD, choroidal neovascularization, generally responds to treatment with anti-vascular endothelial growth factor therapies. Nevertheless, there are no current therapies to restore lost vision in eyes with advanced atrophic AMD. Oral supplementation with the Age-Related Eye Disease Study (AREDS) or AREDS2 formulation (antioxidant vitamins C and E, lutein, zeaxanthin, and zinc) has been shown to reduce the risk of progression to advanced AMD, although the impact was in neovascular rather than atrophic AMD. Recent findings, however, have demonstrated several features of early AMD that are likely to be druggable targets for treatment. Studies have established that much of the genetic risk for AMD is associated with complement genes. Consequently, several complement-based therapeutic treatment approaches are being pursued. Potential treatment strategies against AMD deposit formation and protein and/or lipid deposition will be discussed, including anti-amyloid therapies. In addition, the role of autophagy in AMD and prevention of oxidative stress through modulation of the antioxidant system will be explored. Finally, the success of these new therapies in clinical trials and beyond relies on early detection, disease typing, and predicting disease progression, areas that are currently being rapidly transformed by improving imaging modalities and functional assays.

  14. Dry Age-Related Macular Degeneration: Mechanisms, Therapeutic Targets, and Imaging

    Science.gov (United States)

    Bowes Rickman, Catherine; Farsiu, Sina; Toth, Cynthia A.; Klingeborn, Mikael

    2013-01-01

    Age-related macular degeneration is the leading cause of irreversible visual dysfunction in individuals over 65 in Western Society. Patients with AMD are classified as having early stage disease (early AMD), in which visual function is affected, or late AMD (generally characterized as either “wet” neovascular AMD, “dry” atrophic AMD or both), in which central vision is severely compromised or lost. Until recently, there have been no therapies available to treat the disorder(s). Now, the most common wet form of late-stage AMD, choroidal neovascularization, generally responds to treatment with anti–vascular endothelial growth factor therapies. Nevertheless, there are no current therapies to restore lost vision in eyes with advanced atrophic AMD. Oral supplementation with the Age-Related Eye Disease Study (AREDS) or AREDS2 formulation (antioxidant vitamins C and E, lutein, zeaxanthin, and zinc) has been shown to reduce the risk of progression to advanced AMD, although the impact was in neovascular rather than atrophic AMD. Recent findings, however, have demonstrated several features of early AMD that are likely to be druggable targets for treatment. Studies have established that much of the genetic risk for AMD is associated with complement genes. Consequently, several complement-based therapeutic treatment approaches are being pursued. Potential treatment strategies against AMD deposit formation and protein and/or lipid deposition will be discussed, including anti-amyloid therapies. In addition, the role of autophagy in AMD and prevention of oxidative stress through modulation of the antioxidant system will be explored. Finally, the success of these new therapies in clinical trials and beyond relies on early detection, disease typing, and predicting disease progression, areas that are currently being rapidly transformed by improving imaging modalities and functional assays. PMID:24335072

  15. Application of Emerging Pharmaceutical Technologies for Therapeutic Challenges of Space Exploration Missions

    Science.gov (United States)

    Putcha, Lakshmi

    2011-01-01

    An important requirement of therapeutics for extended duration exploration missions beyond low Earth orbit will be the development of pharmaceutical technologies suitable for sustained and preventive health care in remote and adverse environmental conditions. Availability of sustained, stable and targeted delivery pharmaceuticals for preventive health of major organ systems including gastrointestinal, hepato-renal, musculo-skeletal and immune function are essential to offset adverse effects of space environment beyond low Earth orbit. Specifically, medical needs may include multi-drug combinations for hormone replacement, radiation protection, immune enhancement and organ function restoration. Additionally, extended stability of pharmaceuticals dispensed in space must be also considered in future drug development. Emerging technologies that can deliver stable and multi-therapy pharmaceutical preparations and delivery systems include nanotechnology based drug delivery platforms, targeted-delivery systems in non-oral and non-parenteral formulation matrices. Synthetic nanomaterials designed with molecular precision offer defined structures, electronics, and chemistries to be efficient drug carriers with clear advantages over conventional materials of drug delivery matricies. Nano-carrier materials like the bottle brush polymers may be suitable for systemic delivery of drug cocktails while Superparamagnetic Iron Oxide Nanoparticles or (SPIONS) have great potential to serve as carriers for targeted drug delivery to a specific site. These and other emerging concepts of drug delivery and extended shelf-life technologies will be reviewed in light of their application to address health-care challenges of exploration missions. Innovations in alternate treatments for sustained immune enhancement and infection control will be also discussed.

  16. Towards a methodology to formulate sustainable diets for livestock: accounting for environmental impact in diet formulation.

    Science.gov (United States)

    Mackenzie, S G; Leinonen, I; Ferguson, N; Kyriazakis, I

    2016-05-28

    The objective of this study was to develop a novel methodology that enables pig diets to be formulated explicitly for environmental impact objectives using a Life Cycle Assessment (LCA) approach. To achieve this, the following methodological issues had to be addressed: (1) account for environmental impacts caused by both ingredient choice and nutrient excretion, (2) formulate diets for multiple environmental impact objectives and (3) allow flexibility to identify the optimal nutritional composition for each environmental impact objective. An LCA model based on Canadian pig farms was integrated into a diet formulation tool to compare the use of different ingredients in Eastern and Western Canada. By allowing the feed energy content to vary, it was possible to identify the optimum energy density for different environmental impact objectives, while accounting for the expected effect of energy density on feed intake. A least-cost diet was compared with diets formulated to minimise the following objectives: non-renewable resource use, acidification potential, eutrophication potential, global warming potential and a combined environmental impact score (using these four categories). The resulting environmental impacts were compared using parallel Monte Carlo simulations to account for shared uncertainty. When optimising diets to minimise a single environmental impact category, reductions in the said category were observed in all cases. However, this was at the expense of increasing the impact in other categories and higher dietary costs. The methodology can identify nutritional strategies to minimise environmental impacts, such as increasing the nutritional density of the diets, compared with the least-cost formulation.

  17. Potential Therapeutic Effects of Psilocybin.

    Science.gov (United States)

    Johnson, Matthew W; Griffiths, Roland R

    2017-07-01

    Psilocybin and other 5-hydroxytryptamine 2A agonist classic psychedelics have been used for centuries as sacraments within indigenous cultures. In the mid-twentieth century they were a focus within psychiatry as both probes of brain function and experimental therapeutics. By the late 1960s and early 1970s these scientific inquires fell out of favor because classic psychedelics were being used outside of medical research and in association with the emerging counter culture. However, in the twenty-first century, scientific interest in classic psychedelics has returned and grown as a result of several promising studies, validating earlier research. Here, we review therapeutic research on psilocybin, the classic psychedelic that has been the focus of most recent research. For mood and anxiety disorders, three controlled trials have suggested that psilocybin may decrease symptoms of depression and anxiety in the context of cancer-related psychiatric distress for at least 6 months following a single acute administration. A small, open-label study in patients with treatment-resistant depression showed reductions in depression and anxiety symptoms 3 months after two acute doses. For addiction, small, open-label pilot studies have shown promising success rates for both tobacco and alcohol addiction. Safety data from these various trials, which involve careful screening, preparation, monitoring, and follow-up, indicate the absence of severe drug-related adverse reactions. Modest drug-related adverse effects at the time of medication administration are readily managed. US federal funding has yet to support therapeutic psilocybin research, although such support will be important to thoroughly investigate efficacy, safety, and therapeutic mechanisms.

  18. Yessotoxin, a Promising Therapeutic Tool

    Directory of Open Access Journals (Sweden)

    Amparo Alfonso

    2016-01-01

    Full Text Available Yessotoxin (YTX is a polyether compound produced by dinoflagellates and accumulated in filter feeding shellfish. No records about human intoxications induced by this compound have been published, however it is considered a toxin. Modifications in second messenger levels, protein levels, immune cells, cytoskeleton or activation of different cellular death types have been published as consequence of YTX exposure. This review summarizes the main intracellular pathways modulated by YTX and their pharmacological and therapeutic implications.

  19. Cell kinetics and therapeutic efficiency

    International Nuclear Information System (INIS)

    Andreeff, M.; Abenhardt, W.; Gruner, B.; Stoffner, D.; Mainz Univ.

    1976-01-01

    The study shows that cell kinetics effects correlate with the effects of cytostatic drugs in the tumour model investigated here. It should, however, be noted that even genetically related tumour cell types may react differently to the same cytostatic drug, and that the cell kinetics effects, due to the changes in the cell cycle, cannot be predicted but should be followed with a very fast method, e.g. sequential flan fluorescence cytophotometry, for optimal therapeutic results. (orig./GSE) [de

  20. Control of Black Rot Disease in Tomato Fruits by Using Formulated Ginger Essential oil Treated by Gamma Radiation

    International Nuclear Information System (INIS)

    Helal, I.M.; Abdeldaiem, M.H.

    2008-01-01

    Ginger essential oil (Zingiber officinale) treated by gamma radiation at dose of 10 kGy was selected as an active ingredient for formulation of the biocide. Liquid formulations (emulsifiable concentrates) were prepared using different emulsifiers (Emulgator B.L.M. and tween 80 or tween 20) and additive oil (soybean oil). Physicochemical properties of the formulated oil (spontaneous emulsification, emulsion stability; cold stability and heat stability, viscosity, surface tension and ph) were measured. The formulated oil was tested in vivo to investigate its efficiency for controlling the growth of Alternaria alternata inoculated into tomato fruits. The results indicated that soaking inoculated tomato fruits in the formulated oil (ginger essential oil + soybean oil + emulgator B.L.M. + tween 80) treatment at concentration of 300 ppm for a period of 12 minute was the most effective for controlling the growth of the tested fungus. In addition, the formulated oil had efficiency for controlling the rot development on tomato fruits when applied as therapeutic and protective agents