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  Subjects -> CHEMISTRY (Total: 837 journals)
    - ANALYTICAL CHEMISTRY (48 journals)
    - CHEMISTRY (586 journals)
    - CRYSTALLOGRAPHY (22 journals)
    - ELECTROCHEMISTRY (26 journals)
    - INORGANIC CHEMISTRY (41 journals)
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    - PHYSICAL CHEMISTRY (68 journals)

CHEMISTRY (586 journals)            First | 1 2 3 4 5 6 | Last

Journal of Catalysts     Open Access  
Journal of Chemical & Engineering Data     Full-text available via subscription   (Followers: 11)
Journal of Chemical and Biological Interfaces     Full-text available via subscription  
Journal of Chemical Education     Full-text available via subscription   (Followers: 17)
Journal of Chemical Health Risks     Open Access   (Followers: 2)
Journal of Chemical Information and Modeling     Full-text available via subscription   (Followers: 6)
Journal of Chemical Research     Full-text available via subscription   (Followers: 5)
Journal of Chemical Science and Technology     Open Access   (Followers: 3)
Journal of Chemical Sciences     Partially Free   (Followers: 17)
Journal of Chemical Theory and Computation     Full-text available via subscription   (Followers: 13)
Journal of Cheminformatics     Open Access   (Followers: 1)
Journal of Chemistry     Open Access   (Followers: 3)
Journal of Chemometrics     Hybrid Journal   (Followers: 10)
Journal of Chromatography A     Hybrid Journal   (Followers: 53)
Journal of Chromatography Library     Full-text available via subscription   (Followers: 5)
Journal of Clinical Toxicology     Open Access   (Followers: 1)
Journal of Colloid and Interface Science     Hybrid Journal   (Followers: 14)
Journal of Computational Chemistry     Hybrid Journal   (Followers: 15)
Journal of Coordination Chemistry     Hybrid Journal   (Followers: 1)
Journal of Dispersion Science and Technology     Hybrid Journal  
Journal of Encapsulation and Adsorption Sciences     Open Access   (Followers: 4)
Journal of Environmental Chemistry and Ecotoxicology     Open Access   (Followers: 2)
Journal of Flow Chemistry     Full-text available via subscription   (Followers: 1)
Journal of Fluorescence     Hybrid Journal   (Followers: 4)
Journal of Fluorine Chemistry     Hybrid Journal   (Followers: 6)
Journal of Fuel Chemistry and Technology     Full-text available via subscription   (Followers: 5)
Journal of Great Lakes Research     Hybrid Journal   (Followers: 7)
Journal of Heterocyclic Chemistry     Hybrid Journal   (Followers: 5)
Journal of Immunoassay and Immunochemistry     Hybrid Journal   (Followers: 3)
Journal of Inclusion Phenomena and Macrocyclic Chemistry     Hybrid Journal   (Followers: 1)
Journal of Inorganic Biochemistry     Hybrid Journal   (Followers: 2)
Journal of Labelled Compounds and Radiopharmaceuticals     Hybrid Journal   (Followers: 1)
Journal of Macromolecular Science, Part A: Pure and Applied Chemistry     Hybrid Journal   (Followers: 3)
Journal of Mass Spectrometry     Hybrid Journal   (Followers: 24)
Journal of Materials Chemistry A : Materials for Energy and Sustainability     Full-text available via subscription   (Followers: 22)
Journal of Materials Chemistry B : Materials for Biology and Medicine     Full-text available via subscription   (Followers: 5)
Journal of Materials Chemistry C : Materials for Optical, Magnetic and Electronic Devices     Full-text available via subscription   (Followers: 5)
Journal of Materials Physics and Chemistry     Open Access  
Journal of Materials Research     Full-text available via subscription   (Followers: 10)
Journal of Mathematical Chemistry     Hybrid Journal   (Followers: 6)
Journal of Medicinal Chemistry     Full-text available via subscription   (Followers: 86)
Journal of Membrane and Separation Technology     Hybrid Journal  
Journal of Membrane Science     Hybrid Journal   (Followers: 11)
Journal of Modern Chemistry & Chemical Technology     Full-text available via subscription   (Followers: 2)
Journal of Molecular Catalysis A: Chemical     Hybrid Journal   (Followers: 3)
Journal of Molecular Graphics and Modelling     Hybrid Journal   (Followers: 4)
Journal of Molecular Liquids     Hybrid Journal   (Followers: 1)
Journal of Molecular Modeling     Hybrid Journal   (Followers: 3)
Journal of Molecular Recognition     Hybrid Journal   (Followers: 2)
Journal of Molecular Spectroscopy     Hybrid Journal   (Followers: 7)
Journal of Molecular Structure     Hybrid Journal   (Followers: 3)
Journal of Nanoparticles     Open Access  
Journal of Nanostructure in Chemistry     Open Access   (Followers: 3)
Journal of Natural Gas Chemistry     Full-text available via subscription   (Followers: 2)
Journal of Nepal Chemical Society     Open Access  
Journal of Nucleic Acids Investigation     Open Access   (Followers: 2)
Journal of Ocean University of China (English Edition)     Hybrid Journal   (Followers: 1)
Journal of Organometallic Chemistry     Hybrid Journal   (Followers: 13)
Journal of Photochemistry and Photobiology A: Chemistry     Hybrid Journal   (Followers: 4)
Journal of Photochemistry and Photobiology C: Photochemistry Reviews     Full-text available via subscription   (Followers: 3)
Journal of Polymer & Composites     Full-text available via subscription   (Followers: 3)
Journal of Polymer and Biopolymer Physics Chemistry     Open Access   (Followers: 2)
Journal of Polymer Science Part A: Polymer Chemistry     Hybrid Journal   (Followers: 124)
Journal of Polymers     Open Access   (Followers: 1)
Journal of Porphyrins and Phthalocyanines     Hybrid Journal   (Followers: 2)
Journal of Pure and Applied Chemistry Research     Open Access   (Followers: 1)
Journal of Raman Spectroscopy     Hybrid Journal   (Followers: 11)
Journal of Research Updates in Polymer Science     Hybrid Journal  
Journal of Saudi Chemical Society     Open Access  
Journal of Solid State Chemistry     Hybrid Journal   (Followers: 14)
Journal of Solution Chemistry     Hybrid Journal   (Followers: 4)
Journal of Structural Chemistry     Hybrid Journal  
Journal of Sulfur Chemistry     Hybrid Journal   (Followers: 2)
Journal of Superhard Materials     Hybrid Journal   (Followers: 1)
Journal of Surfactants and Detergents     Hybrid Journal   (Followers: 5)
Journal of Systems Chemistry     Open Access  
Journal of Taibah University for Science     Open Access  
Journal of the American Chemical Society     Full-text available via subscription   (Followers: 211)
Journal of the American Society for Mass Spectrometry     Hybrid Journal   (Followers: 21)
Journal of the American Society of Brewing Chemists     Full-text available via subscription   (Followers: 1)
Journal of the Bangladesh Chemical Society     Open Access  
Journal of the Chilean Chemical Society     Open Access   (Followers: 1)
Journal of the Iranian Chemical Society     Hybrid Journal  
Journal of the Korean Society for Applied Biological Chemistry     Hybrid Journal   (Followers: 1)
Journal of the Mexican Chemical Society     Open Access   (Followers: 1)
Journal of Theoretical and Computational Chemistry     Hybrid Journal   (Followers: 8)
Journal of Theoretical Chemistry     Open Access  
Journal of Wood Chemistry and Technology     Hybrid Journal   (Followers: 7)
JPC - Journal of Planar Chromatography - Modern TLC     Full-text available via subscription   (Followers: 5)
Jurnal Penelitian Sains (JPS)     Open Access  
Jurnal Teknologi Informasi     Open Access   (Followers: 3)
Karbala International Journal of Modern Science     Open Access  
Kinetics and Catalysis     Hybrid Journal   (Followers: 3)
Korea-Australia Rheology Journal     Hybrid Journal  
Langmuir     Full-text available via subscription   (Followers: 42)
Latvian Journal of Chemistry     Open Access   (Followers: 1)
Lebensmittelchemie     Hybrid Journal   (Followers: 1)
Lipid Insights     Open Access  
Luminescence     Hybrid Journal   (Followers: 1)
Macromolecular Materials & Engineering     Hybrid Journal   (Followers: 5)

  First | 1 2 3 4 5 6 | Last

  Pharmaceuticals
  [SJR: 0.585]   [H-I: 16]   [5 followers]  Follow
    
  This is an Open Access Journal Open Access journal
   ISSN (Print) 1424-8247
   Published by MDPI Homepage  [140 journals]
  • Pharmaceuticals, Vol. 8, Pages 366-415: Peptides and Peptidomimetics for
           Antimicrobial Drug Design

    • Authors: Biljana Mojsoska, Håvard Jenssen
      Pages: 366 - 415
      Abstract: The purpose of this paper is to introduce and highlight a few classes of traditional antimicrobial peptides with a focus on structure-activity relationship studies. After first dissecting the important physiochemical properties that influence the antimicrobial and toxic properties of antimicrobial peptides, the contributions of individual amino acids with respect to the peptides antibacterial properties are presented. A brief discussion of the mechanisms of action of different antimicrobials as well as the development of bacterial resistance towards antimicrobial peptides follows. Finally, current efforts on novel design strategies and peptidomimetics are introduced to illustrate the importance of antimicrobial peptide research in the development of future antibiotics.
      PubDate: 2015-07-13
      DOI: 10.3390/ph8030366
      Issue No: Vol. 8, No. 3 (2015)
       
  • Pharmaceuticals, Vol. 8, Pages 416-434: Toxicological Studies of 212Pb
           

    • Authors: Diane Milenic, Alfredo Molinolo, María Solivella, Eileen Banaga, Julien Torgue, Sarah Besnainou, Martin Brechbiel, Kwamena Baidoo
      Pages: 416 - 434
      Abstract: Faced with the novelty of a 212Pb-labeled monoclonal antibody (mAb) for clinical translation, concerns were expressed by the Food and Drug Administration (FDA) regarding 212Pb prematurely released from the mAb-chelate conjugate. The objective of this study was to simulate the worst case scenario of such a failure. Groups of Balb/c mice (n = 9–20) were administered 212Pb by intraperitoneal (0.0925–1.85 MBq) or intravenous (0.0925–1.11 MBq) injection and then euthanized at 7 or 90 days to assess acute or chronic effects. Weights were recorded prior to injection of the 212Pb and at the end of the observation periods. Blood samples were collected for clinical chemistry and blood cell analysis. Thirty tissues were harvested and formalin fixed for histopathological examination. Treatment related effects of the 212Pb were observed in the bone marrow, spleen, kidneys and the liver. Histological alterations in these organs were considered mild to moderate, indicating low grade toxicity, and not considered severe enough to affect function. This data was presented to the FDA and determined to be acceptable. The clinical trial with 212Pb-TCMC-trastuzumab was approved in January 2011 and the trial opened at the University of Alabama at Birmingham (UAB) in July.
      PubDate: 2015-07-24
      DOI: 10.3390/ph8030416
      Issue No: Vol. 8, No. 3 (2015)
       
  • Pharmaceuticals, Vol. 8, Pages 151-175: Reactive Oxygen Species,
           Apoptosis, Antimicrobial Peptides and Human Inflammatory Diseases

    • Authors: Babatunji Oyinloye, Abiola Adenowo, Abidemi Kappo
      Pages: 151 - 175
      Abstract: Excessive free radical generation, especially reactive oxygen species (ROS) leading to oxidative stress in the biological system, has been implicated in the pathogenesis and pathological conditions associated with diverse human inflammatory diseases (HIDs). Although inflammation which is considered advantageous is a defensive mechanism in response to xenobiotics and foreign pathogen; as a result of cellular damage arising from oxidative stress, if uncontrolled, it may degenerate to chronic inflammation when the ROS levels exceed the antioxidant capacity. Therefore, in the normal resolution of inflammatory reactions, apoptosis is acknowledged to play a crucial role, while on the other hand, dysregulation in the induction of apoptosis by enhanced ROS production could also result in excessive apoptosis identified in the pathogenesis of HIDs. Apparently, a careful balance must be maintained in this complex environment. Antimicrobial peptides (AMPs) have been proposed in this review as an excellent candidate capable of playing prominent roles in maintaining this balance. Consequently, in novel drug design for the treatment and management of HIDs, AMPs are promising candidates owing to their size and multidimensional properties as well as their wide spectrum of activities and indications of reduced rate of resistance.
      PubDate: 2015-04-02
      DOI: 10.3390/ph8020151
      Issue No: Vol. 8, No. 2 (2015)
       
  • Pharmaceuticals, Vol. 8, Pages 176-185: Edaravone Enhances Brain-Derived
           Neurotrophic Factor Production in the Ischemic Mouse Brain

    • Authors: Satoshi Okuyama, Mayu Morita, Atsushi Sawamoto, Tsukasa Terugo, Mitsunari Nakajima, Yoshiko Furukawa
      Pages: 176 - 185
      Abstract: Edaravone, a clinical drug used to treat strokes, protects against neuronal cell death and memory loss in the ischemic brains of animal models through its antioxidant activity. In the present study, we subcutaneously administrated edaravone to mice (3 mg/kg/day) for three days immediately after bilateral common carotid artery occlusion, and revealed through an immunohistochemical analysis that edaravone (1) accelerated increases in the production of brain-derived neurotrophic factor (BDNF) in the hippocampus; (2) increased the number of doublecortin-positive neuronal precursor cells in the dentate gyrus subgranular zone; and (3) suppressed the ischemia-induced inactivation of calcium-calmodulin-dependent protein kinase II in the hippocampus. We also revealed through a Western blotting analysis that edaravone (4) induced the phosphorylation of cAMP response element-binding (CREB), a transcription factor that regulates BDNF gene expression; and (5) induced the phosphorylation of extracellular signal-regulated kinases 1/2, an upstream signal factor of CREB. These results suggest that the neuroprotective effects of edaravone following brain ischemia were mediated not only by the elimination of oxidative stress, but also by the induction of BDNF production.
      PubDate: 2015-04-02
      DOI: 10.3390/ph8020176
      Issue No: Vol. 8, No. 2 (2015)
       
  • Pharmaceuticals, Vol. 8, Pages 186-195: Does Amifostine Reduce Metabolic
           Rate' Effect of the Drug on Gas Exchange and Acute Ventilatory Hypoxic
           Response in Humans

    • Authors: Jaideep Pandit, Caroline Allen, Evelyn Little, Federico Formenti, Adrian Harris, Peter Robbins
      Pages: 186 - 195
      Abstract: Amifostine is added to chemoradiation regimens in the treatment of many cancers on the basis that, by reducing the metabolic rate, it protects normal cells from toxic effects of therapy. We tested this hypothesis by measuring the metabolic rate (by gas exchange) over 255 min in 6 healthy subjects, at two doses (500 mg and 1000 mg) of amifostine infused over 15 min at the start of the protocol. We also assessed the ventilatory response to six 1 min exposures to isocapnic hypoxia mid-protocol. There was no change in metabolic rate with amifostine as measured by oxygen uptake (p = 0.113). However in carbon dioxide output and respiratory quotient, we detected a small decline over time in control and drug protocols, consistent with a gradual change from carbohydrate to fat metabolism over the course of the relatively long study protocol. A novel result was that amifostine (1000 mg) increased the mean ± SD acute hypoxic ventilatory response from 12.4 ± 5.1 L/min to 20.3 ± 11.9 L/min (p = 0.045). In conclusion, any cellular protective effects of amifostine are unlikely due to metabolic effects. The stimulatory effect on hypoxic ventilatory responses may be due to increased levels of hypoxia inducible factor, either peripherally in the carotid body, or centrally in the brain.
      PubDate: 2015-04-16
      DOI: 10.3390/ph8020186
      Issue No: Vol. 8, No. 2 (2015)
       
  • Pharmaceuticals, Vol. 8, Pages 196-220: Wharton’s Jelly-Derived
           Mesenchymal Stromal Cells as a Promising Cellular Therapeutic Strategy for
           the Management of Graft-versus-Host Disease

    • Authors: Joseph McGuirk, J. Smith, Clint Divine, Micheal Zuniga, Mark Weiss
      Pages: 196 - 220
      Abstract: Allogeneic hematopoietic cell transplantation (allo-HCT), a treatment option in hematologic malignancies and bone marrow failure syndromes, is frequently complicated by Graft-versus-host disease (GVHD). The primary treatment for GVHD involves immune suppression by glucocorticoids. However, patients are often refractory to the steroid therapy, and this results in a poor prognosis. Therefore alternative therapies are needed to treat GVHD. Here, we review data supporting the clinical investigation of a novel cellular therapy using Wharton’s jelly (WJ)-derived mesenchymal stromal cells (MSCs) as a potentially safe and effective therapeutic strategy in the management of GVHD. Adult-derived sources of MSCs have demonstrated signals of efficacy in the management of GVHD. However, there are limitations, including: limited proliferation capacity; heterogeneity of cell sources; lengthy expansion time to clinical dose; expansion failure in vitro; and a painful, invasive, isolation procedure for the donor. Therefore, alternative MSC sources for cellular therapy are sought. The reviewed data suggests MSCs derived from WJ may be a safe and effective cellular therapy for GVHD. Laboratories investigated and defined the immune properties of WJ-MSCs for potential use in cellular therapy. These cells represent a more uniform cell population than bone marrow-derived MSCs, displaying robust immunosuppressive properties and lacking significant immunogenicity. They can be collected safely and painlessly from individuals at birth, rapidly expanded and stored cryogenically for later clinical use. Additionally, data we reviewed suggested licensing MSCs (activating MSCs by exposure to cytokines) to enhance effectiveness in treating GVHD. Therefore, WJCs should be tested as a second generation, relatively homogeneous allogeneic cell therapy for the treatment of GVHD.
      PubDate: 2015-04-16
      DOI: 10.3390/ph8020196
      Issue No: Vol. 8, No. 2 (2015)
       
  • Pharmaceuticals, Vol. 8, Pages 221-229: Design and Synthesis of Novel
           N-Arylsulfonyl-3-(2-yl-ethanone)-6-methylindole Derivatives as Inhibitors
           of HIV-1 Replication

    • Authors: Zhiping Che, Shengming Liu, Yuee Tian, Zhenjie Hu, Yingwu Chen, Genqiang Chen
      Pages: 221 - 229
      Abstract: Seven novel N-arylsulfonyl-3-(2-yl-ethanone)-6-methylindole derivatives 4a–f and 6 were readily synthesized and have been identified as inhibitors of human immunodeficiency virus type-1 (HIV-1) replication. Initial biological studies indicated that among these derivatives, N-(p-ethyl)phenylsulfonyl-3-[2-morpholinoethanone]-6-methylindole (4f) and N-(p-ethyl)phenylsulfonyl-3-[2-(5-phenyl-1,3,4-oxadiazole-2-yl-thio)ethanone]-6-methylindole (6) showed the most promising activity against HIV-1 replication. The effective concentration (EC50) and therapeutic index (TI) values of 4f and 6 were 9.42/4.62 μM, and >49.77/66.95, respectively. The cytotoxicity of these compounds has also been assessed. No significant cytotoxicities were found for any of these compounds.
      PubDate: 2015-05-08
      DOI: 10.3390/ph8020221
      Issue No: Vol. 8, No. 2 (2015)
       
  • Pharmaceuticals, Vol. 8, Pages 230-249: Seatbelts in CAR therapy: How Safe
           Are CARS'

    • Authors: Kentaro Minagawa, Xiaoou Zhou, Shin Mineishi, Antonio Di Stasi
      Pages: 230 - 249
      Abstract: T-cells genetically redirected with a chimeric antigen receptor (CAR) to recognize tumor antigens and kill tumor cells have been infused in several phase 1 clinical trials with success. Due to safety concerns related to on-target/off-tumor effects or cytokine release syndrome, however, strategies to prevent or abate serious adverse events are required. Pharmacologic therapies; suicide genes; or novel strategies to limit the cytotoxic effect only to malignant cells are under active investigations. In this review, we summarize results and toxicities of investigations employing CAR redirected T-cells, with a focus on published strategies to grant safety of this promising cellular application.
      PubDate: 2015-05-08
      DOI: 10.3390/ph8020230
      Issue No: Vol. 8, No. 2 (2015)
       
  • Pharmaceuticals, Vol. 8, Pages 250-256: Immunotherapeutic Applications of
           NK Cells

    • Authors: Carter Davis, David Rizzieri
      Pages: 250 - 256
      Abstract: Natural Killer (NK) cells are lymphoid cells that exhibit an innate response against virus-infected cells. These cells are also capable of mounting an immune response against tumor cells after education through major histocompatibility complex (MHC) class I molecules. NK cell regulation is mediated through IFN-gamma and IL-15, important cytokines which can drive NK cell expansion in vivo. Previous studies have shown effective infusion of allogeneic NK cells after lymphodepleting regimens with induction of remission of poor prognosis acute myeloid leukemia (AML). Challenges remain in the expansion of these NK cells once infused and in their education to recognize tumor targets. A principal mechanism of tumor recognition is through KIR mismatch in cells lacking self MHC I molecules. Activating KIRs exist, though their ligands are unknown at this time. Impacting NK cell expansion and education in vivo has been challenging, and thus far clinical applications of NK cells have shown promise in helping to maintain remission in humans, though this remission has not been maintained. Future efforts to utilize NK cells clinically are focusing on developing more consistency in successful expansion of NK cell and educating them to recognize their tumor targets. Additional efforts to utilize novel antibody-based therapy to engage NK cells to their tumor targets are also in development.
      PubDate: 2015-05-25
      DOI: 10.3390/ph8020250
      Issue No: Vol. 8, No. 2 (2015)
       
  • Pharmaceuticals, Vol. 8, Pages 257-276: Microwave-Assisted Synthesis of a
           MK2 Inhibitor by Suzuki-Miyaura Coupling for Study in Werner Syndrome
           Cells

    • Authors: Mark Bagley, Mohammed Baashen, Irina Chuckowree, Jessica Dwyer, David Kipling, Terence Davis
      Pages: 257 - 276
      Abstract: Microwave-assisted Suzuki-Miyaura cross-coupling reactions have been employed towards the synthesis of three different MAPKAPK2 (MK2) inhibitors to study accelerated aging in Werner syndrome (WS) cells, including the cross-coupling of a 2-chloroquinoline with a 3-pyridinylboronic acid, the coupling of an aryl bromide with an indolylboronic acid and the reaction of a 3-amino-4-bromopyrazole with 4-carbamoylphenylboronic acid. In all of these processes, the Suzuki-Miyaura reaction was fast and relatively efficient using a palladium catalyst under microwave irradiation. The process was incorporated into a rapid 3-step microwave-assisted method for the synthesis of a MK2 inhibitor involving 3-aminopyrazole formation, pyrazole C-4 bromination using N-bromosuccinimide (NBS), and Suzuki-Miyaura cross-coupling of the pyrazolyl bromide with 4-carbamoylphenylboronic acid to give the target 4-arylpyrazole in 35% overall yield, suitable for study in WS cells.
      PubDate: 2015-06-03
      DOI: 10.3390/ph8020257
      Issue No: Vol. 8, No. 2 (2015)
       
  • Pharmaceuticals, Vol. 8, Pages 277-278: Pharmaceuticals Best Paper Award
           2015

    • Authors: Jean Eynde
      Pages: 277 - 278
      Abstract: It is always a difficult task for a jury to classify articles from a selection of outstanding manuscripts. [...]
      PubDate: 2015-06-05
      DOI: 10.3390/ph8020277
      Issue No: Vol. 8, No. 2 (2015)
       
  • Pharmaceuticals, Vol. 8, Pages 279-302: Synthesis, Biological Evaluation
           and Molecular Modeling of Substituted Indeno[1,2-b]indoles as Inhibitors
           of Human Protein Kinase CK2

    • Authors: Faten Alchab, Laurent Ettouati, Zouhair Bouaziz, Andre Bollacke, Jean-Guy Delcros, Christoph Gertzen, Holger Gohlke, Noël Pinaud, Mathieu Marchivie, Jean Guillon, Bernard Fenet, Joachim Jose, Marc Borgne
      Pages: 279 - 302
      Abstract: Due to their system of annulated 6-5-5-6-membered rings, indenoindoles have sparked great interest for the design of ATP-competitive inhibitors of human CK2. In the present study, we prepared twenty-one indeno[1,2-b]indole derivatives, all of which were tested in vitro on human CK2. The indenoindolones 5a and 5b inhibited human CK2 with an IC50 of 0.17 and 0.61 µM, respectively. The indeno[1,2-b]indoloquinone 7a also showed inhibitory activity on CK2 at a submicromolar range (IC50 = 0.43 µM). Additionally, a large number of indenoindole derivatives was evaluated for their cytotoxic activities against the cell lines 3T3, WI-38, HEK293T and MEF.
      PubDate: 2015-06-08
      DOI: 10.3390/ph8020279
      Issue No: Vol. 8, No. 2 (2015)
       
  • Pharmaceuticals, Vol. 8, Pages 303-320: X-Linked Dilated Cardiomyopathy: A
           Cardiospecific Phenotype of Dystrophinopathy

    • Authors: Akinori Nakamura
      Pages: 303 - 320
      Abstract: X-linked dilated cardiomyopathy (XLDCM) is a distinct phenotype of dystrophinopathy characterized by preferential cardiac involvement without any overt skeletal myopathy. XLDCM is caused by mutations of the Duchenne muscular dystrophy (DMD) gene and results in lethal heart failure in individuals between 10 and 20 years. Patients with Becker muscular dystrophy, an allelic disorder, have a milder phenotype of skeletal muscle involvement compared to Duchenne muscular dystrophy (DMD) and sometimes present with dilated cardiomyopathy. The precise relationship between mutations in the DMD gene and cardiomyopathy remain unclear. However, some hypothetical mechanisms are being considered to be associated with the presence of some several dystrophin isoforms, certain reported mutations, and an unknown dystrophin-related pathophysiological mechanism. Recent therapy for Duchenne muscular dystrophy, the severe dystrophinopathy phenotype, appears promising, but the presence of XLDCM highlights the importance of focusing on cardiomyopathy while elucidating the pathomechanism and developing treatment.
      PubDate: 2015-06-09
      DOI: 10.3390/ph8020303
      Issue No: Vol. 8, No. 2 (2015)
       
  • Pharmaceuticals, Vol. 8, Pages 321-336: A Critical Review of Alpha
           Radionuclide Therapy—How to Deal with Recoiling Daughters'

    • Authors: Robin de Kruijff, Hubert Wolterbeek, Antonia Denkova
      Pages: 321 - 336
      Abstract: This review presents an overview of the successes and challenges currently faced in alpha radionuclide therapy. Alpha particles have an advantage in killing tumour cells as compared to beta or gamma radiation due to their short penetration depth and high linear energy transfer (LET). Touching briefly on the clinical successes of radionuclides emitting only one alpha particle, the main focus of this article lies on those alpha-emitting radionuclides with multiple alpha-emitting daughters in their decay chain. While having the advantage of longer half-lives, the recoiled daughters of radionuclides like 224Ra (radium), 223Ra, and 225Ac (actinium) can do significant damage to healthy tissue when not retained at the tumour site. Three different approaches to deal with this problem are discussed: encapsulation in a nano-carrier, fast uptake of the alpha emitting radionuclides in tumour cells, and local administration. Each approach has been shown to have its advantages and disadvantages, but when larger activities need to be used clinically, nano-carriers appear to be the most promising solution for reducing toxic effects, provided there is no accumulation in healthy tissue.
      PubDate: 2015-06-10
      DOI: 10.3390/ph8020321
      Issue No: Vol. 8, No. 2 (2015)
       
  • Pharmaceuticals, Vol. 8, Pages 337-350: Tryptophan Breakdown in Patients
           with HCV Infection is Influenced by IL28B Polymorphism

    • Authors: Heinz Zoller, Annina Jenal, Albert Staettermayer, Sebastian Schroecksnadel, Peter Ferenci, Dietmar Fuchs
      Pages: 337 - 350
      Abstract: Until recently, the standard treatment of chronic hepatitis C virus (HCV) infection was a combination therapy with PEG-IFN-α plus ribavirin. Previous studies have proven that several markers predict the outcome of such therapy, e.g., pretreatment plasma levels of interferon inducible protein IP-10, HCV RNA and IL28B-related single nucleotide polymorphisms (SNP). Altered activity of tryptophan metabolizing enzyme indoleamine 2,3-dioxygenase (IDO) has been also shown in patients suffering from HCV infection. In this study, we investigated whether IL28B SNP in patients infected with HCV is related to the tryptophan breakdown rate. Before therapy, serum tryptophan and kynurenine concentrations were determined in 25 patients with established HCV infection and the kynurenine to tryptophan ratio (KYN/TRP) was calculated as an estimate of the tryptophan breakdown rate. In parallel, neopterin and nitrite concentrations were determined. A significant difference of serum KYN/TRP existed between the three IL28B polymorphism groups: C/C genotype had the highest and T/T genotype had the lowest KYN/TRP (p < 0.05). Likewise, C/C genotype was associated with higher KYN/TRP than non-C/C genotype (p = 0.01). There was a smaller difference between the three groups regarding the absolute kynurenine concentrations, the C/C genotype being associated with higher kynurenine concentrations. None of the other comparisons revealed any statistical significance. In conclusion, patients with C/C genotype presented with the highest tryptophan breakdown rate already before antiretroviral therapy with IFN-α/ribavirin. The differences in tryptophan metabolism might relate to HCV clearance and also to side effects of IFN-α therapy.
      PubDate: 2015-06-18
      DOI: 10.3390/ph8020337
      Issue No: Vol. 8, No. 2 (2015)
       
  • Pharmaceuticals, Vol. 8, Pages 351-365: Effects of a Formula Containing
           Two Types of Prebiotics, Bifidogenic Growth Stimulator and
           Galacto-oligosaccharide, and Fermented Milk Products on Intestinal
           Microbiota and Antibody Response to Influenza Vaccine in Elderly Patients:
           A Randomized Controlled Trial

    • Authors: Shinya Nagafuchi, Taketo Yamaji, Akihiro Kawashima, Yukiko Saito, Takeshi Takahashi, Takayuki Yamamoto, Mitsuo Maruyama, Hiroyasu Akatsu
      Pages: 351 - 365
      Abstract: We investigated the effect of a formula containing two different prebiotics (bifidogenic growth stimulator and galacto-oligosaccharide) and fermented milk products on intestinal microbiota and antibody responses to an influenza vaccine in enterally fed elderly in-patients. Patients were administered either formula containing prebiotics and fermented milk products (group F: n = 12, 79.9 ± 9.5 years old) or standard formula (group C: n = 12, 80.7 ± 10.1 years old) via percutaneous endoscopic gastrostomy during a 14-week intervention period. Subjects were immunized with an influenza vaccine (A/H1N1, A/H3N2, and B) at week 4 of the intervention. Blood biochemical indices, intestinal bacteria populations and antibody titers were analyzed. Bifidobacterium counts increased significantly in group F compared with group C. The enhanced antibody titers against A/H1N1 were maintained in group F for a longer period compared with group C. The titers against A/H3N2 were unchanged between both groups, and those against B were significantly lower in group F than in group C, although few subjects had seroprotective titers against A/H3N2 and B. These results suggest that administration of the formula containing prebiotics and fermented milk products may maintain antibody titers for longer periods through the improvement of intestinal microbiota.
      PubDate: 2015-06-18
      DOI: 10.3390/ph8020351
      Issue No: Vol. 8, No. 2 (2015)
       
  • Pharmaceuticals, Vol. 8, Pages 38-39: Acknowledgement to Reviewers of
           Pharmaceuticals in 2014

    • Authors: Pharmaceuticals Office
      Pages: 38 - 39
      Abstract: The editors of Pharmaceuticals would like to express their sincere gratitude to the following reviewers for assessing manuscripts in 2014:[...]
      PubDate: 2015-01-08
      DOI: 10.3390/ph8010038
      Issue No: Vol. 8, No. 1 (2015)
       
  • Pharmaceuticals, Vol. 8, Pages 40-61: γδ T Cell
           Immunotherapy—A Review

    • Authors: Hirohito Kobayashi, Yoshimasa Tanaka
      Pages: 40 - 61
      Abstract: Cancer immunotherapy utilizing Vγ9Vδ2 T cells has been developed over the past decade. A large number of clinical trials have been conducted on various types of solid tumors as well as hematological malignancies. Vγ9Vδ2 T cell-based immunotherapy can be classified into two categories based on the methods of activation and expansion of these cells. Although the in vivo expansion of Vγ9Vδ2 T cells by phosphoantigens or nitrogen-containing bisphosphonates (N-bis) has been translated to early-phase clinical trials, in which the safety of the treatment was confirmed, problems such as activation-induced Vγ9Vδ2 T cell anergy and a decrease in the number of peripheral blood Vγ9Vδ2 T cells after infusion of these stimulants have not yet been solved. In addition, it is difficult to ex vivo expand Vγ9Vδ2 T cells from advanced cancer patients with decreased initial numbers of peripheral blood Vγ9Vδ2 T cells. In this article, we review the clinical studies and reports targeting Vγ9Vδ2 T cells and discuss the development and improvement of Vγ9Vδ2 T cell-based cancer immunotherapy.
      PubDate: 2015-02-12
      DOI: 10.3390/ph8010040
      Issue No: Vol. 8, No. 1 (2015)
       
  • Pharmaceuticals, Vol. 8, Pages 62-106: Hitting the Bull’s-Eye in
           Metastatic Cancers—NSAIDs Elevate ROS in Mitochondria, Inducing
           Malignant Cell Death

    • Authors: Stephen Ralph, Rhys Pritchard, Sara Rodríguez-Enríquez, Rafael Moreno-Sánchez, Raymond Ralph
      Pages: 62 - 106
      Abstract: Tumor metastases that impede the function of vital organs are a major cause of cancer related mortality. Mitochondrial oxidative stress induced by hypoxia, low nutrient levels, or other stresses, such as genotoxic events, act as key drivers of the malignant changes in primary tumors to enhance their progression to metastasis. Emerging evidence now indicates that mitochondrial modifications and mutations resulting from oxidative stress, and leading to OxPhos stimulation and/or enhanced reactive oxygen species (ROS) production, are essential for promoting and sustaining the highly metastatic phenotype. Moreover, the modified mitochondria in emerging or existing metastatic cancer cells, by their irreversible differences, provide opportunities for selectively targeting their mitochondrial functions with a one-two punch. The first blow would block their anti-oxidative defense, followed by the knockout blow—promoting production of excess ROS, capitulating the terminal stage—activation of the mitochondrial permeability transition pore (mPTP), specifically killing metastatic cancer cells or their precursors. This review links a wide area of research relevant to cellular mechanisms that affect mitochondria activity as a major source of ROS production driving the pro-oxidative state in metastatic cancer cells. Each of the important aspects affecting mitochondrial function are discussed including: hypoxia, HIFs and PGC1 induced metabolic changes, increased ROS production to induce a more pro-oxidative state with reduced antioxidant defenses. It then focuses on how the mitochondria, as a major source of ROS in metastatic cancer cells driving the pro-oxidative state of malignancy enables targeting drugs affecting many of these altered processes and why the NSAIDs are an excellent example of mitochondria-targeted agents that provide a one-two knockout activating the mPTP and their efficacy as selective anticancer metastasis drugs.
      PubDate: 2015-02-13
      DOI: 10.3390/ph8010062
      Issue No: Vol. 8, No. 1 (2015)
       
  • Pharmaceuticals, Vol. 8, Pages 107-122: A Retrospective Study of the
           Impact of 21-Gene Recurrence Score Assay on Treatment Choice in Node
           Positive Micrometastatic Breast Cancer

    • Authors: Thomas Frazier, Kevin Fox, J. Smith, Christine Laronga, Anita McSwain, Devchand Paul, Michael Schultz, Joseph Stilwill, Christine Teal, Tracey Weisberg, Judith Vacchino, Amy Sing, Dasha Cherepanov, Wendy Hsiao, Eunice Chang, Michael Broder
      Pages: 107 - 122
      Abstract: To assess clinical utility of the 21-gene assay (Oncotype DX® Recurrence Score®), we determined whether women with HER2(−)/ER+ pN1mi breast cancer with low (<18) Recurrence Scores results are given adjuvant chemotherapy in a lower proportion than those with high scores (≥31). This was a multicenter chart review of ≥18 year old women with pN1mi breast cancer, HER2(−)/ER+ tumors, ductal/lobular/mixed histology, with the assay ordered on or after 1 January 2007. One hundred and eighty one patients had a mean age of 60.7 years; 82.9% had ECOG performance status 0; 33.7% had hypertension, 22.7% had osteoporosis, 18.8% had osteoarthritis, and 8.8% had type-2 diabetes. Mean Recurrence Score was 17.8 (range: 0–50). 48.6% had a mastectomy; 55.8% had a lumpectomy. 19.8% of low-risk group patients were recommended chemotherapy vs. 57.9% in the intermediate-risk group and 100% in the high-risk group (p < 0.001). A total of 80.2% of the low-risk group were recommended endocrine therapy alone, while 77.8% of the high-risk group were recommended both endocrine and chemotherapy (p < 0.001). The Oncotype DX Recurrence Score result provides actionable information that can be incorporated into treatment planning for women with HER2(−)/ER+ pN1mi breast cancer. The Recurrence Score result has clinical utility in treatment planning for HER2(−)/ER+ pN1mi breast cancer patients.
      PubDate: 2015-03-17
      DOI: 10.3390/ph8010107
      Issue No: Vol. 8, No. 1 (2015)
       
  • Pharmaceuticals, Vol. 8, Pages 123-150: Antimicrobial Peptides in 2014

    • Authors: Guangshun Wang, Biswajit Mishra, Kyle Lau, Tamara Lushnikova, Radha Golla, Xiuqing Wang
      Pages: 123 - 150
      Abstract: This article highlights new members, novel mechanisms of action, new functions, and interesting applications of antimicrobial peptides reported in 2014. As of December 2014, over 100 new peptides were registered into the Antimicrobial Peptide Database, increasing the total number of entries to 2493. Unique antimicrobial peptides have been identified from marine bacteria, fungi, and plants. Environmental conditions clearly influence peptide activity or function. Human α-defensin HD-6 is only antimicrobial under reduced conditions. The pH-dependent oligomerization of human cathelicidin LL-37 is linked to double-stranded RNA delivery to endosomes, where the acidic pH triggers the dissociation of the peptide aggregate to release its cargo. Proline-rich peptides, previously known to bind to heat shock proteins, are shown to inhibit protein synthesis. A model antimicrobial peptide is demonstrated to have multiple hits on bacteria, including surface protein delocalization. While cell surface modification to decrease cationic peptide binding is a recognized resistance mechanism for pathogenic bacteria, it is also used as a survival strategy for commensal bacteria. The year 2014 also witnessed continued efforts in exploiting potential applications of antimicrobial peptides. We highlight 3D structure-based design of peptide antimicrobials and vaccines, surface coating, delivery systems, and microbial detection devices involving antimicrobial peptides. The 2014 results also support that combination therapy is preferred over monotherapy in treating biofilms.
      PubDate: 2015-03-23
      DOI: 10.3390/ph8010123
      Issue No: Vol. 8, No. 1 (2015)
       
 
 
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