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  Subjects -> ENVIRONMENTAL STUDIES (Total: 766 journals)
    - ENVIRONMENTAL STUDIES (702 journals)
    - POLLUTION (22 journals)
    - TOXICOLOGY AND ENVIRONMENTAL SAFETY (33 journals)
    - WASTE MANAGEMENT (9 journals)

ENVIRONMENTAL STUDIES (702 journals)                  1 2 3 4 5 6 7 8 | Last

Acta Ecologica Sinica     Open Access   (Followers: 9)
Acta Limnologica Brasiliensia     Open Access   (Followers: 2)
Acta Oecologica     Hybrid Journal   (Followers: 9)
Acta Regionalia et Environmentalica     Open Access  
Administration and Policy in Mental Health and Mental Health Services Research     Partially Free   (Followers: 11)
Advances in Ecological Research     Full-text available via subscription   (Followers: 24)
Advances in Environmental Sciences - International Journal of the Bioflux Society     Open Access   (Followers: 24)
Advances in Life Science and Technology     Open Access   (Followers: 5)
Aeolian Research     Hybrid Journal   (Followers: 1)
African Journal of Environmental Science and Technology     Open Access   (Followers: 2)
African Journal of Sustainable Development     Full-text available via subscription   (Followers: 3)
AGE     Hybrid Journal   (Followers: 4)
Age and Ageing     Hybrid Journal   (Followers: 23)
Agricultura Tecnica     Open Access   (Followers: 5)
Agro-Science     Full-text available via subscription  
Agronomy for Sustainable Development     Hybrid Journal   (Followers: 10)
Ambiência     Open Access  
Ambiente & Agua : An Interdisciplinary Journal of Applied Science     Open Access   (Followers: 1)
Ambiente & sociedade     Open Access   (Followers: 2)
American Journal of Applied Sciences     Open Access   (Followers: 27)
American Journal of Environmental Engineering     Open Access   (Followers: 6)
American Journal of Environmental Protection     Open Access   (Followers: 3)
American Journal of Environmental Sciences     Open Access   (Followers: 13)
American Journal of Microbiology     Open Access   (Followers: 13)
American Naturalist     Full-text available via subscription   (Followers: 36)
Annals of Environmental Science     Open Access   (Followers: 9)
Annals of GIS     Hybrid Journal   (Followers: 14)
Annals of Warsaw University of Life Sciences - SGGW. Land Reclamation     Open Access   (Followers: 2)
Annual Review of Ecology, Evolution, and Systematics     Full-text available via subscription   (Followers: 36)
Annual Review of Environment and Resources     Full-text available via subscription   (Followers: 14)
Annual Review of Pharmacology and Toxicology     Full-text available via subscription   (Followers: 18)
Annual Review of Resource Economics     Full-text available via subscription   (Followers: 10)
Applied and Environmental Soil Science     Open Access   (Followers: 12)
Applied Ecology and Environmental Sciences     Open Access   (Followers: 7)
Applied Environmental Education & Communication     Hybrid Journal   (Followers: 11)
Aquatic Ecology     Hybrid Journal   (Followers: 13)
Aquatic Toxicology     Hybrid Journal   (Followers: 17)
Archives des Maladies Professionnelles et de l'Environnement     Full-text available via subscription   (Followers: 1)
Archives of Environmental and Occupational Health     Hybrid Journal   (Followers: 5)
Archives of Environmental Contamination and Toxicology     Hybrid Journal   (Followers: 10)
Archives of Environmental Protection     Open Access   (Followers: 4)
Archives of Toxicology     Hybrid Journal   (Followers: 10)
Asia Pacific Journal of Environment Ecology and Sustainable Development     Open Access   (Followers: 1)
Asian Journal of Earth Sciences     Open Access   (Followers: 17)
Asian Journal of Rural Development     Open Access   (Followers: 9)
ATBU Journal of Environmental Technology     Open Access  
Atmospheric and Climate Sciences     Open Access   (Followers: 14)
Atmospheric Environment     Hybrid Journal   (Followers: 27)
Austral Ecology     Hybrid Journal   (Followers: 7)
Australasian Journal of Environmental Management     Hybrid Journal   (Followers: 4)
Australasian Journal of Human Security, The     Full-text available via subscription   (Followers: 3)
Australian Journal of Environmental Education     Full-text available via subscription   (Followers: 6)
Basic & Clinical Pharmacology & Toxicology     Hybrid Journal   (Followers: 6)
Basic and Applied Ecology     Hybrid Journal   (Followers: 13)
Behavioral Ecology     Hybrid Journal   (Followers: 33)
Behavioral Ecology and Sociobiology     Hybrid Journal   (Followers: 27)
Biodegradation     Hybrid Journal   (Followers: 2)
Biodiversity     Hybrid Journal   (Followers: 16)
Biofouling: The Journal of Bioadhesion and Biofilm Research     Hybrid Journal   (Followers: 3)
Bioremediation Journal     Hybrid Journal   (Followers: 5)
BioRisk     Open Access   (Followers: 2)
BMC Ecology     Open Access   (Followers: 15)
Boston College Environmental Affairs Law Review     Open Access   (Followers: 5)
Bothalia : African Biodiversity & Conservation     Open Access  
Built Environment     Full-text available via subscription   (Followers: 4)
Bulletin of Environmental Contamination and Toxicology     Hybrid Journal   (Followers: 11)
Bulletin of the American Meteorological Society     Open Access   (Followers: 12)
Canadian Journal of Earth Sciences     Full-text available via subscription   (Followers: 7)
Canadian Journal of Remote Sensing     Full-text available via subscription   (Followers: 12)
Canadian Journal of Soil Science     Full-text available via subscription   (Followers: 12)
Canadian Water Resources Journal     Hybrid Journal   (Followers: 17)
Capitalism Nature Socialism     Hybrid Journal   (Followers: 10)
Casopis Slezskeho Zemskeho Muzea - serie A - vedy prirodni     Open Access  
CCLR - Carbon and Climate Law Review     Full-text available via subscription   (Followers: 2)
Cell Biology and Toxicology     Hybrid Journal   (Followers: 8)
Chain Reaction     Full-text available via subscription  
Chemical Research in Toxicology     Full-text available via subscription   (Followers: 14)
Chemico-Biological Interactions     Hybrid Journal   (Followers: 2)
Chemosphere     Hybrid Journal   (Followers: 10)
Child and Adolescent Mental Health     Hybrid Journal   (Followers: 18)
Civil and Environmental Research     Open Access   (Followers: 11)
CLEAN - Soil, Air, Water     Hybrid Journal   (Followers: 14)
Clean Technologies and Environmental Policy     Hybrid Journal   (Followers: 8)
Climate Change Economics     Hybrid Journal   (Followers: 16)
Climate Policy     Hybrid Journal   (Followers: 18)
Coastal Engineering Journal     Hybrid Journal   (Followers: 1)
Columbia Journal of Environmental Law     Free   (Followers: 7)
Computational Ecology and Software     Open Access   (Followers: 6)
Computational Water, Energy, and Environmental Engineering     Open Access   (Followers: 1)
Conservation and Society     Open Access   (Followers: 6)
Conservation Letters     Hybrid Journal   (Followers: 18)
Conservation Physiology     Open Access  
Conservation Science     Open Access   (Followers: 8)
Construction Innovation: Information, Process, Management     Hybrid Journal   (Followers: 13)
Contemporary Problems of Ecology     Hybrid Journal   (Followers: 2)
Continental Journal of Environmental Design and Management     Open Access   (Followers: 4)
Continental Journal of Renewable Energy     Open Access   (Followers: 8)
Continental Journal of Sustainable Development     Open Access   (Followers: 9)
Creativity and Innovation Management     Hybrid Journal   (Followers: 140)
Critical Reviews in Environmental Science and Technology     Hybrid Journal   (Followers: 7)

        1 2 3 4 5 6 7 8 | Last

Journal Cover Basic & Clinical Pharmacology & Toxicology
   [8 followers]  Follow    
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
     ISSN (Print) 1742-7835 - ISSN (Online) 1742-7843
     Published by John Wiley and Sons Homepage  [1602 journals]   [SJR: 0.588]   [H-I: 56]
  • Development of Clinical Pharmacology as a Medical Speciality in Europe
           – The Roles of WHO, IUPHAR and EACPT
    • Authors: Folke Sjöqvist
      Abstract: Clinical pharmacology has now existed as a teaching and research discipline for nearly 50 years, but with notable exceptions, it is not yet established in many countries as a medical speciality. This MiniReview describes the attempts of IUPHAR, WHO and EACPT to involve clinical pharmacology in the global efforts to improve the use of medicines towards increased efficacy and safety. The MiniReview emphasizes the situation in Europe. This article is protected by copyright. All rights reserved.
      PubDate: 2014-06-21T01:48:14.063358-05:
      DOI: 10.1111/bcpt.12278
       
  • Loading Dose of Fomepizole is Safe in Children with Presumed Toxic Alcohol
           Exposure ‐ A Case Series
    • Authors: Dimitri Frémont; Marie‐Pierre Berleur, Bruno Mégarbane
      Abstract: Fomepizole, a potent alcohol dehydrogenase inhibitor was shown to be an effective and safe antidote for treating toxic alcohol poisoning in adults [1]. However, evidence for its effectiveness and safety in children remains limited [2]. We reviewed the records of children treated with fomepizole sulfate (Fomepizole AP‐HP®), the only marketed product in France, manufactured and distributed by the state pharmaceutical agency for Paris hospitals (AGEPS). This article is protected by copyright. All rights reserved.
      PubDate: 2014-06-18T06:39:39.664038-05:
      DOI: 10.1111/bcpt.12276
       
  • Saquinavir‐NO inhibits IL‐6 production in macrophages
    • Authors: Miljana Momčilović; Katia Mangano, Bojan Jevtić, Santa Mammana, Stanislava Stošić‐Grujičić, Ferdinando Nicoletti, Djordje Miljković
      Abstract: Covalent attachment of the nitric oxide (NO) moiety to the HIV protease inhibitor Saquinavir (Saq) produced a new chemical entity, named Saquinavir‐NO (Saq‐NO) with reduced toxicity and potent immunoregulatory influence on T lymphocytes. In this study, we have compared head to head the effects of Saq‐NO and Saq on mouse and rat peritoneal macrophage cytokine secretion and NO production upon in vitro, ex vivo and in vivo conditions. The results demonstrate that Saq‐NO, but not Saq, potently decreased interleukin (IL)‐10, IL‐6 and nitrite accumulation and increased the levels of IL‐1β and tumour necrosis factor (TNF) in supernatants of mouse and rat macrophage cultures in vitro. Treatment of mice with Saq‐NO, but not Saq, inhibited ex vivo secretion of IL‐6 from macrophages. Consistent with these findings, Saq‐NO also reduced blood levels of IL‐6 in lipopolysaccharide‐treated mice. The observed inhibitory influence of Saq‐NO on IL‐6 generation in macrophages may be involved in the observed anti‐tumour and immunomodulatory effects of the drug. This article is protected by copyright. All rights reserved.
      PubDate: 2014-06-18T06:37:01.267126-05:
      DOI: 10.1111/bcpt.12268
       
  • Arctigenin Promotes Apoptosis in Ovarian Cancer Cells via the
           iNOS/NO/STAT3/Survivin Signalling
    • Authors: Ke Huang; Li‐an Li, Yuan‐guang Meng, Yan‐qin You, Xiao‐yu Fu, Lei Song
      Abstract: Arctigenin is a biologically active lignan extracted from the seeds of Arctium lappa and shows anti‐cancer activity against a variety of human cancers. The aim of this study was to determine the effects of arctigenin on ovarian cancer cell proliferation and survival and associated molecular mechanisms. Human ovarian cancer OVCAR3 and SKOV3 cells were treated with arctigenin, and cell proliferation and apoptosis were assessed. Western blot analysis was used to examine signal transducer and activator of transcription‐3 (STAT3) phosphorylation and survivin and inducible nitric oxide synthase (iNOS) expression. The involvement of STAT3/survivin/iNOS/NO signalling in arctigenin action was checked. Arctigenin treatment resulted in a significant and dose‐dependent inhibition of cell proliferation. Arctigenin‐treated cells showed a 4‐6‐fold increase in the percentage of apoptosis, compared to control cells. Pre‐treatment with Ac‐DEVD‐CHO, a specific inhibitor of caspase‐3, counteracted the induction of apoptosis by arctigenin. Arctigenin treatment significantly inhibited STAT3 phosphorylation and survivin and iNOS expression. Arctigenin‐induced apoptosis was impaired by pre‐transfection with survivin‐expressing plasmid or addition of chemical nitric oxide (NO) donors. Additionally, exogenous NO prevented the suppression of STAT3 phosphorylation and survivin expression by arctigenin. Arctigenin treatment inhibits the proliferation and induces caspase‐3‐dependent apoptosis of ovarian cancer cells. Suppression of iNOS/NO/STAT3/survivin signalling is causally linked to the anti‐cancer activity of arctigenin. Therefore, arctigenin may be applicable to anti‐cancer therapy for ovarian cancer. This article is protected by copyright. All rights reserved.
      PubDate: 2014-06-17T22:01:23.437668-05:
      DOI: 10.1111/bcpt.12270
       
  • Modulation of Imatinib Cytotoxicity by Selenite in HCT116 Colorectal
           Cancer Cells
    • Authors: Amal Kamal Abdel‐Aziz; Samar Saad Eldeen Azab, Samar Samir Youssef, Abeer Mostafa El‐Sayed, Ebtehal El‐Demerdash, Samia Shouman
      Pages: n/a - n/a
      Abstract: Imatinib is a principal therapeutic agent for targeting colorectal tumours. However, mono‐targeting by imatinib does not always achieve complete cancer eradication. Selenite, a well‐known chemopreventive agent, is commonly used in cancer patients. In the current study, we aimed to explore whether selenite can modulate imatinib cytotoxicity in colorectal cancer cells. HCT116 cells were treated with different concentrations of imatinib and/or selenite for 24, 48 and 72 hr. Imatinib‐selenite interaction was analysed using isobologram equation. As indicators of apoptosis, DNA fragmentation, caspase‐3 activity, Bcl‐2 expression were explored. Autophagic machinery was also checked by visualizing acidic vesicular organelles and measuring Beclin‐1 expression. Furthermore, reactive oxygen and nitrogen species were also examined. The present study demonstrated that selenite synergistically augmented imatinib cytotoxicity in HCT116 cells as evidenced by combination and dose reduction indices. Supranutritional dose of selenite when combined with imatinib induced apoptotic machinery by decreasing Bcl‐2 expression, increasing caspase‐3 activity and subsequently fragmenting DNA and blunted cytoprotective autophagy by decreasing Beclin‐1 expression and autophagosomes formation. Moreover, their combination induced cell cycle S phase block, increased total thiol content and reduced nitric oxide levels. In conclusion, selenite synergizes imatinib cytotoxicity through multi‐barrelled molecular targeting, providing a novel therapeutic approach for colorectal cancer. This article is protected by copyright. All rights reserved.
      PubDate: 2014-06-13T08:38:22.371008-05:
      DOI: 10.1111/bcpt.12281
       
  • 8‐O‐Acetyl Shanzhiside Methylester Attenuates Cerebral
           Ischemia/Reperfusion Injury through an Anti‐Inflammatory Mechanism
           in Diabetic Rats
    • Authors: Liang Zhang; Ze‐Chun Kan, Xiu‐Li Zhang, Han Fang, Wang‐Lin Jiang
      Abstract: Inflammatory activation plays a vital role in the pathophysiologic mechanisms of stroke and diabetes mellitus (DM), exerts the deleterious effects on the progression of the brain and leads to vascular damage in diabetic stroke. The objectives of this study were to investigate the effects of 8‐O‐acetyl shanzhiside methylester (ND01) on tumour necrosis factor‐α (TNF‐α) stimulated SH‐SY5Y cell line in vitro and the experimental ischaemic diabetic stroke model in vivo. For TNF‐α stimulated SH‐SY5Y cells, pre‐incubated with ND01, then analyze protein expression. For in vivo experiment, the diabetic rats were subjected to middle cerebral artery occlusion (MCAO) for 30 min. followed by reperfusion for 23 hr. Treatment of SH‐SY5Y cells with ND01 blocked TNF‐α‐induced nuclear transcription factor κB (NF‐κB) activation, and decreased high‐mobility group box1 (HMGB1) expression. ND01 40 mg/kg demonstrated significant neuroprotective effect even after delayed administration at 4 hr after I/R. ND01 40 mg/kg attenuated the histopathological damage, decreased brain swelling, inhibited NF‐κB activation and reduced HMGB1 expression in ischaemic brain tissue. These data show that ND01 protects diabetic brain against I/R injury with a favourable therapeutic time‐window by alleviating diabetic cerebral I/R injury and attenuating blood‐brain barrier (BBB) breakdown, and its protective effects may involve HMGB1 and NF‐κB signalling pathway. This article is protected by copyright. All rights reserved.
      PubDate: 2014-06-10T05:01:00.083775-05:
      DOI: 10.1111/bcpt.12266
       
  • Inosine Strongly Enhances Human C32 Melanoma Cells Proliferation through
           PLC‐PKC‐MEK1/2‐ERK1/2 and PI3K Pathways
    • Authors: Ana Sofia Soares; Vera Marisa Costa, Carmen Diniz, Paula Fresco
      Abstract: Malignant melanoma is the most deadly type of skin cancer. The lack of effective pharmacological approaches could be related to the incomplete understanding of the pathophysiological mechanisms involved in cell melanoma proliferation. Adenosine has growth‐promoting and growth‐inhibitory effects on tumour cells. We aimed to investigate effects of adenosine and its metabolic product, inosine, on human C32 melanoma cells and the signalling pathways involved. The 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) reduction and bromodeoxyuridine (BrdU) proliferation assays were used to evaluate adenosine, adenosine deaminase and inosine effects, in the absence or presence of AR, A3AR and P2Y1R antagonists; and PLC, PKC, MEK1/2 and PI3K inhibitors. ERK1/2 levels were determined using an ELISA kit. Adenosine and inosine levels were quantified using an enzyme‐coupled assay. Adenosine caused cell proliferation through AR activation. Adenosine deaminase increased inosine levels (nanomolar concentrations) on the extracellular space, in a time‐dependent manner, inducing proliferation through A3AR activation. Micromolar concentrations of inosine enhanced proliferation through A3AR activation, causing an increase in ERK1/2 levels, and P2Y1R activation via ENT‐dependent mechanisms. We propose the simultaneous activation of PLC‐PKC‐MEK1/2‐ERK1/2 and PI3K pathways as the main mechanism responsible for the proliferative effect elicited by inosine and its significant role in melanoma cancer progression. This article is protected by copyright. All rights reserved.
      PubDate: 2014-06-06T10:30:48.910118-05:
      DOI: 10.1111/bcpt.12280
       
  • The Evaluation of Prophylactic Efficacy of Newly Developed Reversible
           Inhibitors of Acetylcholinesterase in Soman‐Poisoned Mice – A
           Comparison with commonly used Pyridostigmine
    • Authors: Jiri Kassa; Jan Korabecny, Vendula Sepsova, Martina Tumova
      Abstract: The ability of four newly developed reversible inhibitors of acetylcholinesterase (PC‐37, PC‐48, JaKo 39, JaKo 40) and currently available carbamate pyridostigmine to increase the resistance of mice against soman and the efficacy of antidotal treatment of soman‐poisoned mice was evaluated and compared. No reversible inhibitor of acetylcholinesterase studied was able to decrease the LD50 value of soman in mice. Thus, the pharmacological pre‐treatment with pyridostigmine or newly synthesized inhibitors of acetylcholinesterase was not able to significantly protect mice against soman‐induced lethal acute toxicity. In addition, neither pyridostigmine nor new reversible inhibitors of acetylcholinesterase was able to increase the efficacy of antidotal treatment (the oxime HI‐6 in combination with atropine) of soman‐poisoned mice. These findings demonstrate that pharmacological pre‐treatment of soman‐poisoned mice with tested reversible inhibitors of acetylcholinesterase is not promising. This article is protected by copyright. All rights reserved.
      PubDate: 2014-06-06T03:37:27.413623-05:
      DOI: 10.1111/bcpt.12269
       
  • Riccardin D, a Macrocyclic Bisbibenzy, Inhibits Human Breast Cancer Growth
           through the Suppression of Telomerase Activity
    • Authors: Cui‐Cui Sun; Hui‐Min Xu, Yi Yuan, Zu‐Hua Gao, Hong‐Xiang Lou, Xian‐Jun Qu
      Abstract: Riccardin D, a liverwort‐derived naturally occurring macrocyclic bisbibenzyl, has been found to exert anticancer effects in multiple cancer cell types. In this study, we investigated the effect and mechanism of Riccardin D on human breast cancer. Experiments were performed on human breast cancer MCF‐7 and MDA‐MB‐231 cells. The antitumour effects of Riccardin D were assessed by the 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyltetrazolium bromide (MTT) assay and human breast cancer xenografts mice model. TRAPeze® XL Telomerase Detection assay was used for the detection of telomerase activity. γ‐H2AX foci formation was tested for the induction of DNA damage response. Cell cycle distribution was analysed by flow cytometry and cell apoptosis was determined by Annexin V‐FITC/PI staining, terminal deoxynucleotidyl transferase‐mediated dUTP nick end labeling (TUNEL) assay and western blotting. Riccardin D effectively inhibited the growth of MCF‐7 and MDA‐MB‐231 cells in vitro. And Riccardin D also effectively delayed the growth of MCF‐7 and MDA‐MB‐231‐luc‐D3H2LN xenografts without significant loss of body weight. Further analysis suggested that Riccardin D's effects may arise from its suppression of telomerase activity, which led to telomere dysfunction. Telomerase inhibition and telomere dysfunction could activate the canonical ATM kinase‐mediated DNA damage response, as shown by elevated expression of γ‐H2AX, p‐ATM and p‐Chk2. This is finally followed by the induction of cell cycle arrest and apoptosis, as shown by the increase of TUNEL stained cells, caspase activation, PARP cleavage and the increase of bax/bcl‐2 ratio. Moreover, Riccardin D induced p53‐proficient MCF‐7 cells to arrest in G1 phase and p53‐deficient MDA‐MB‐231 cells to arrest in G2/M phase. Overall, these results demonstrate that Riccardin D may inhibit human breast cancer growth through suppression of telomerase activity. This article is protected by copyright. All rights reserved.
      PubDate: 2014-06-06T02:46:22.042794-05:
      DOI: 10.1111/bcpt.12267
       
  • Stimulation of Erythrocyte Cell Membrane Scrambling by Nystatin
    • Authors: Abaid Malik; Rosi Bissinger, Kashif Jilani, Florian Lang
      Abstract: The antifungal ionophore nystatin dissipates the Na+ and K+ gradients across the cell membrane leading to cellular gain of Na+ and cellular loss of K+. The increase of cellular Na+ concentration may result in Ca2+ accumulation in exchange for Na+. Increase of cytosolic Ca2+ activity ([Ca2+]i) and loss of cellular K+ fosters apoptosis‐like suicidal erythrocyte death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling leading to phosphatidylserine‐exposure at the erythrocyte surface. The present study explored whether nystatin stimulates eryptosis. Cell volume was estimated from forward scatter, phosphatidylserine‐exposure from annexin V binding and [Ca2+]i from Fluo3‐fluorescence in flow cytometry. A 48‐hr exposure to nystatin (15 μg/ml) was followed by a significant increase of [Ca2+]i, a significant increase of annexin V binding and a significant decrease of forward scatter. The annexin V binding following nystatin treatment was significantly blunted in the nominal absence of extracellular Ca2+. Partial replacement of extracellular Na+ with extracellular K+ blunted the nystatin‐induced erythrocyte shrinkage but increased [Ca2+]i and annexin V binding. Nystatin triggers cell membrane scrambling, an effect at least partially due to entry of extracellular Ca2+. This article is protected by copyright. All rights reserved.
      PubDate: 2014-06-03T04:10:28.514081-05:
      DOI: 10.1111/bcpt.12279
       
  • Adjuvant Anticholinesterase Therapy for the Management of
           Epilepsy‐inducedMemory Deficit:A Critical Preclinical Study
    • Authors: Awanish Mishra; Rajesh Kumar Goel
      Abstract: Epilepsy is one of the major neurological disorders still awaiting safer drugs with improved antiepileptic effect and lesser side effects. Apart from epilepsy itself, AEDs also have been shown to induce cognitive impairment in patients with epilepsy. There are limited data for the treatment of this menace. As cholinergic approach has widely been practiced for the restoration of memory in various neurodegenerative disorders, hence this study was envisaged to evaluate add on effect of acetylcholinesterase inhibitor (tacrine) with phenytoin in pentylenetetrazole‐kindling induced learning and memory deficit in mice. In this study, mice were kindled using subconvulsive dose of pentylenetetrazole (35 mg/kg, i.p.; at interval of 48±2 hr) andsuccessfully kindled animals were divided into different groups and treated with vehicle, phenytoinand phenytoinin combination with tacrine (0.3 mg/kg), atropine (1 mg/kg) and tacrine + atropine. Effect of different interventions on learning and memory was evaluated using elevated plus maze and passive shock avoidance on days 5, 10, 15 and 20. Phenytoin‐treated kindled animals were associated with learning and memory deficit, while tacrinesupplementation improved memory deficit with increased seizure severity score. Atropine treatment significantly reversed the protective effect of tacrine. Neurochemical findingsalso support the behavioural finding of the study. Our results suggest the use of anticholinesterases, with better seizuretolerance, for the management of cognitive impairment of epilepsy, as adjunct therapy. This article is protected by copyright. All rights reserved.
      PubDate: 2014-05-30T00:08:22.880888-05:
      DOI: 10.1111/bcpt.12275
       
  • Pharmacogenetics, Plasma Concentrations, Clinical Signs and EEG during
           Propofol Treatment
    • Authors: Muhammad Suleman Khan; Eva‐Lena Zetterlund, Henrik Gréen, Anna Oscarsson, Anna‐Lena Zackrisson, Eva Svanborg, Maj‐Lis Lindholm, Harald Persson, Christina Eintrei
      Abstract: A variety of techniques have been developed to monitor the depth of anaesthesia. Propofol's pharmacokinetics and response vary greatly, which might be explained by genetic polymorphisms. We investigated the impact of genetic variations on dosage, anaesthetic depth, and recovery after total intravenous anaesthesia with propofol. A total of 101 patients were enrolled in the study. The plasma concentration of propofol during anaesthesia was measured using high‐performance liquid chromatography. EEG was monitored during the surgical procedure as a measure of anaesthetic depth. Pyrosequencing was used to determine genetic polymorphisms in CYP2B6, CYP2C9, the UGTIA9‐promotor and the GABRE gene. The correlation between genotype and to plasma concentration at the time of loss of consciousness (LOC), the total induction dose, the time to anaesthesia, eye opening and clearance were investigated. EEG monitoring showed that the majority of the patients had not reached a sufficient level of anaesthetic depth (sub‐delta) at the time of loss of consciousness despite a high induction dose of propofol. Patients with UGT1A9‐331C/T had a higher propofol clearance than those without (p=0.03) and required a higher induction dose (p=0.03). The patients with UGT1A9 ‐1818T/C required a longer time to LOC (p=0.03). The patients with CYP2C9*2 had a higher concentration of propofol at the time of LOC (p=0.02). The polymorphisms in the metabolizing enzymes and the receptor could not explain the large variation seen in the pharmacokinetics of propofol and the clinical response seen. At LOC, the patients showed a large difference in EEG pattern. This article is protected by copyright. All rights reserved.
      PubDate: 2014-05-28T11:40:31.061649-05:
      DOI: 10.1111/bcpt.12277
       
  • Geraniol Blocks Calcium And Potassium Channels In The Mammalian
           Myocardium: Useful Effects To Treat Arrhythmias
    • Authors: José Evaldo Rodrigues Menezes‐Filho; Antônio Nei Santana Gondim, Jader Santos Cruz, Américo Azevedo Souza, José Nilson Andrade dos Santos, Eduardo Antônio Conde‐Garcia, Damião Pergentino Sousa, Michel Santana Santos, Evaleide Diniz Oliveira, Carla Maria Lins Vasconcelos
      Abstract: Geraniol is a monoterpene present in several essential oils and it is known to have a plethora of pharmacological activities. In this study, we explored the contractile and electrophysiological properties of geraniol and its antiarrhythmic effects in the heart. The geraniol effects on atrial contractility, L‐type Ca2+ current, K+ currents, action potential (AP) parameters, ECG profile and on the arrhythmia induced by ouabain were evaluated. In the atrium, geraniol reduced the contractile force (~98%, EC = 1,510 ± 160 μM) and diminished the positive inotropism of CaCl2 and BAY K8644. In cardiomyocytes, the ICa,L was reduced by 50.7% (n = 5) after perfusion with 300 μM geraniol. Moreover, geraniol prolonged the AP duration (APD) measured at 50% (n = 5) after repolarization, without changing the resting potential. The increased APD could be attributed to the blockade of the transient outward K+ current (Ito) (59.7%, n = 4), the non‐inactivation K+ current (Iss) (39.2%, n = 4), and the inward rectifier K+ current (IK1) (33.7%, n = 4). In isolated hearts, geraniol increased PRi and QTi without affecting the QRS complex (n = 6), and it reduced both the left ventricular pressure (83%) and heart rate (16.5%). Geraniol delayed the time to onset of ouabain‐induced arrhythmias by 128%, preventing 30% of the increase in resting tension (n = 6). Geraniol exerts its negative inotropic and chronotropic responses in the heart by decreasing both L‐type Ca2+ and voltage‐gated K+ currents, ultimately acting against ouabain‐induced arrhythmias. This article is protected by copyright. All rights reserved.
      PubDate: 2014-05-26T23:47:14.898932-05:
      DOI: 10.1111/bcpt.12274
       
  • Adverse Drug Reactions Causing Hospital Admissions in Childhood: A
           Prospective, Observational, Single‐Centre Study
    • Authors: Petra Langerová; Jiří Vrtal, Karel Urbánek
      Abstract: Adverse drug reactions (ADRs) are common problems in both paediatric and adult medicine. The aim of this study was to prospectively identify the ADRs causing hospital admission of children and identification of the risk factors and involved drugs. The study was performed at the University Hospital in Olomouc, Czech Republic. All patients aged 19 years or under admitted to hospital were included in the study, and all admissions for ADRs were prospectively screened for a period of nine months. Suspected ADRs were subsequently evaluated in detail and causality assessment was undertaken to determine whether each suspected reaction was possible, probable or definite. The assessment of ADR causality was performed using the Naranjo algorithm, the Liverpool ADR Causality Assessment Tool and the Edwards & Aronson causality assessment method. During the study period, 2,903 admissions were identified; of these, there were 143 admissions of patients with an oncological disease. Sixty‐four admissions (2.2%) were caused by an ADR. Anticancer chemotherapy accounted for 35% of the cases, followed by antibiotics (18%), immunosuppressants and vaccines (9% each). The use of different scoring systems does not lead to differences in the numbers of ADRs diagnosed but may result in differences in the determination of the level of certainty. ADRs cause a substantial proportion of children's hospital admissions. The majority of the ADRs diagnosed affected the hematopoietic and gastrointestinal systems; the drugs most frequently involved were cytotoxic agents and antibiotics. The most important risk factors identified were female sex and oncological disease. This article is protected by copyright. All rights reserved.
      PubDate: 2014-05-26T04:58:07.26363-05:0
      DOI: 10.1111/bcpt.12264
       
  • Anti‐metastatic Effects of Licochalcone B on Human Bladder
           CarcinomaT24 by Inhibition of MMP‐9 and NF‐кB Activity
    • Authors: Hong Zhao; Xuan Yuan, Jiangtao Jiang, Penglong Wang, Xiling Sun, Dong Wang, Qiusheng Zheng
      Abstract: This study investigated the mechanisms by which licochalcone B (LCB) inhibits the adhesion,invasion and metastasis of human malignant bladder cancer T24 cells. Cell viability was evaluated using a sulforhodamine B (SRB) assay. Cell migration and invasion ability was conducted using wound‐healing assay and matrigel transwell invasion assay. The activities of matrix metalloproteinases (MMP)‐2 and MMP‐9 were measured by gelatin zymography protease assays. The expression in protein level of NF‐κBP65 and AP‐1 was determined using the ELISA method; the protein levels of MMP‐9, NF‐κBP65, IκBα and P‐IκBα were detected by Western blot. The expression in mRNA level of MMP‐9 was assessed using quantitative real‐time polymerase chain reaction (PCR) and reverse transcription‐PCR. The results indicated that LCB attenuated T24 cell migration, adhesion and invasion in a concentration‐dependent manner. LCB treatment down‐regulated the mRNA expression, protein expression and activity of matrix metalloproteinases (MMP)‐9 but had no effect on MMP‐2. In addition, LCB treatment decreased the protein level of NF‐кBP65 and nuclear translocation of NF‐кB. These findings suggested that LCB attenuated bladder cancer T24 cells migration, adhesion and invasion accompanied with down‐regulation protein expression of MMP‐9 and the nuclear translocation of NF‐кB, Our results provide support that LCB may be a potent adjuvant therapeutic agent in the prevention and therapy of bladder cancer. This article is protected by copyright. All rights reserved.
      PubDate: 2014-05-26T01:45:19.979319-05:
      DOI: 10.1111/bcpt.12273
       
  • Effects of Colistin on the Sensory Nerve Conduction Velocity and
           F‐wave in Mice
    • Authors: Chongshan Dai; Shusheng Tang, Jichang Li, Jiping Wang, Xilong Xiao
      Abstract: The aim of this study was to examine the changes of sensory nerve conduction velocity (SNCV) and F‐wave for colistin‐induced peripheral neurotoxicity using a mouse model. Mice were administered with colistin 5, 7.5 and 15 mg/kg/d via a 3‐min. intravenous infusion. The sensory nerve conduction velocity (SNCV) and F‐wave were measured using the bipolar recording electrodes. The SNCV and F‐wave latency changed in a dose‐ and time‐dependent manner. The significant increase of F‐wave latency and significant decrease of SNCV appeared on day 3 (p < 0.05 and 0.01, respectively) in the 15 mg/kg/d group, and they were markedly changed on day 7 in the 7.5 mg/kg/d (p < 0.01 and 0.05, respectively) and 15 mg/kg/d groups (both p < 0.01). In addition, F‐wave latency also significantly increased on day 7 in the 5 mg/kg/d group (p < 0.05) without any clinical signs. These results indicate that SNCV and F‐wave latency were more sensitive in colistin‐induced neurotoxicity in mice, which highlights the early monitoring tool of polymyxins neurotoxicity in the clinic. This article is protected by copyright. All rights reserved.
      PubDate: 2014-05-26T01:45:18.839703-05:
      DOI: 10.1111/bcpt.12272
       
  • [3H]‐L685,458 Binding Sites are abundant in Multiple Peripheral
           Organs in Rats: Implications for Safety Assessment of Putative
           γ‐secretase Targeting Drugs
    • Authors: Zhi‐Ying Yang; Jian‐Ming Li, Ling Xiao, Lin Mou, Yan Cai, He Huang, Xue‐Gang Luo, Xiao‐Xin Yan
      Abstract: γ‐Secretase is a multimeric enzyme complex that carries out proteolytic processing to a variety of cellular proteins. It is currently explored as a therapeutic target for Alzheimer's disease (AD) and cancer. Mechanism‐based toxicity needs to be thoroughly evaluated for γ‐secretase inhibitory and/or modulatory drugs. The present study comparatively assessed putative γ‐secretase catalytic sites in rat peripheral tissues relative to brain, and explored an effort of its pharmacological inhibition on hair regeneration. Using [3H]‐labeled L685,458, a potent γ‐secretase inhibitor, as probe, we found more abundant presence of γ‐secretase binding sites in the liver, gastrointestinal tract, hair follicle, pituitary gland, ovary and testis, as compared to the brain. Local application of L658,458 delayed vibrissal regrowth following whisker removal. These results suggest that γ‐secretase may execute important biological functions in many peripheral systems, as in the brain. The development of γ‐secretase inhibitors/modulators for AD and cancer therapy should include close monitoring of toxicological panels for hepatic, gastrointestinal, endocrinal and reproductive functions. This article is protected by copyright. All rights reserved.
      PubDate: 2014-05-26T01:45:17.906861-05:
      DOI: 10.1111/bcpt.12271
       
  • Chemotherapy‐Induced Polyneuropathy: Major Agents and Assessment by
           Questionnaires
    • Authors: Ahmed H. Zedan; Ole J. Vilholm
      Abstract: Chemotherapy‐induced polyneuropathy (CIPN) is a common, but underestimated, clinical challenge. Incidence varies depending on many factors that are equally as important as the type of chemotherapeutic agent itself. Moreover, the assessment of CIPN is still uncertain, as several of the most frequently used scales do not rely on a formal neurological evaluation and depend on patients’ reports and examiners’ interpretations. Therefore, the aim of this MiniReview is to introduce the most common chemotherapies that cause neuropathy, and in addition to this, highlight the most significant differences between the neuropathic pain scales, which are most commonly used for assessing CIPN. Polyneuropathy induced by chemotherapies is often described as ‘Chemotherapy‐induced polyneuropathy’(CIPN). CIPN is frequently recorded in patients treated with platinum drugs, Antitubulins, Thalidomide and Bortezomib, representing one of the most severe and potentially dose‐limiting non‐haematological toxic side effects. CIPN commonly occurs in 30 ‐ 40% of patients, but its incidence can vary from 0 ‐ 70% [1].In a significant proportion of patients, CIPN severity can progress months after the discontinuation of treatment, a phenomenon known as ‘coasting’ [2]. This MiniReview will discuss the main features of the CIPN regarding clinical presentation with an overview of the most commonly used scales in the assessment of the CIPN. This article is protected by copyright. All rights reserved.
      PubDate: 2014-05-24T02:00:44.865425-05:
      DOI: 10.1111/bcpt.12262
       
  • Evidence for Involvement of Spinal RANTES in the Antinociceptive Effects
           
    • Authors: Li‐Hua Hang; Shu‐Na Li, Dong‐Hua Shao, Zheng Chen, Yuan‐Feng Chen, Wei‐Wei Shu
      Abstract: It has been shown that triptolide has beneficial effects in the treatment of neuropathic pain but its effects on bone cancer pain (BCP) remain unclear. In the present study, we aimed to explore the potential role of spinal regulated on activation normal T cell expressed and secreted (RANTES) in the antinociceptive effects of triptolide on BCP. A BCP model was induced by injecting Walker 256 mammary gland carcinoma cells into the intramedullary space of rat tibia. Intrathecal administration of triptolide (0.5, 1, 2 μg) could dose‐dependently alleviate mechanical hyperalgesia and spontaneous pain. In addition, there were also concomitant decreases in RANTES mRNA and protein expression levels in spinal dorsal horn. These results suggest that the antinociceptive effects of triptolide are related with inhibition of spinal RANTES expression in BCP rats. The findings of this study may provide a promising drug for the treatment of BCP. This article is protected by copyright. All rights reserved.
      PubDate: 2014-05-24T02:00:18.986428-05:
      DOI: 10.1111/bcpt.12265
       
  • Population Pharmacokinetic Meta‐Analysis of Vortioxetine in Healthy
           Subjects
    • Authors: Johan Areberg; Kamilla B. Petersen, Grace Chen, Himanshu Naik
      Abstract: The objective was to describe the pharmacokinetics of vortioxetine and evaluate the effect of intrinsic and extrinsic factors in the healthy population. Data from 26 clinical pharmacology studies were pooled. A total of 21758 vortioxetine quantifiable plasma concentrations were collected from 887 subjects with corresponding demography. The doses ranged from 2.5‐75 mg (single dose) and 2.5‐60 mg (multiple QD doses). The pharmacokinetics of vortioxetine was best characterized by a two‐compartment model with first‐order absorption, lag‐time and linear elimination, with inter‐individual error terms for absorption rate constant, oral clearance and central volume of distribution. The population mean was 32.7 L/h for oral clearance and 1.97∙103 L for the central volume of distribution. The average elimination half‐life was 65.8 hr. CYP2D6 inferred metabolic status (ultra, extensive, intermediate or poor metabolisers) and age on oral clearance and height on central volume of distribution were identified as statistically significant co‐variate‐parameter relationships. For CYP2D6 poor metabolisers, CL/F was approximately 50% to that seen in CYP2D6 extensive metabolisers. The impact of height on V2/F and age on CL/F was low and not considered to be clinically relevant. The final model was found to be reliable, stable and predictive. A reliable, stable and predictive pharmacokinetic model was developed to characterize pharmacokinetics of vortioxetine in the healthy population. This article is protected by copyright. All rights reserved.
      PubDate: 2014-05-22T05:35:34.499314-05:
      DOI: 10.1111/bcpt.12256
       
  • Drug‐Induced Peripheral Neuropathy
    • Authors: Ole J. Vilholm; Alex A. Christensen, Ahmed H. Zedan, Mustapha Itani
      Abstract: Peripheral neuropathy can be caused by medication, and various descriptions have been applied for this condition. In this MiniReview, the term ‘drug‐induced peripheral neuropathy’ (DIPN) is used with the suggested definition: Damage to nerves of the peripheral nervous system caused by a chemical substance used in the treatment, cure, prevention or diagnosis of a disease. Optic neuropathy is included in this definition. A distinction between DIPN and other aetiologies of peripheral neuropathy is often quite difficult and thus, the aim of this MiniReview is to discuss the major agents associated with DIPN. This article is protected by copyright. All rights reserved.
      PubDate: 2014-05-19T23:38:20.601385-05:
      DOI: 10.1111/bcpt.12261
       
  • Influence of UGT2B7, OPRM1 and ABCB1 Gene Polymorphisms on Morphine Use
    • Authors: Salumeh Bastami; Anil Gupta, Anna‐Lena Zackrisson, Johan Ahlner, Abdimajid Osman, Srinivas Uppugunduri
      Abstract: Therapeutic modulation of pain with morphine and other opioids is associated with significant variation in both effects and adverse effects in individual patients. Many factors including gene polymorphisms have been shown to contribute to the interindividual variability in the response to opioids. The aim of this study was to investigate the significance of UGT2B7, OPRM1 and ABCB1 polymorphisms for interindividual variability in morphine‐induced analgesia in patients undergoing hysterectomy. The frequency of these polymorphisms was also investigated in forensic autopsies as morphine is also a very commonly abused drug. Blood samples were collected from 40 patients following abdominal hysterectomy, 24 hr after initiation of analgesia through a patient‐controlled analgesia (PCA) pump. Samples were genotyped and analysed for morphine and its metabolites. We also genotyped approximately 200 autopsies and found positive for morphine in routine forensic analysis. Patients homozygous for UGT2B7 802C needed significantly lower dose of morphine for pain relief. The same trend was observed for patients homozygous for ABCB1 1236T and 3435T, as well as to OPRM1 118A. The dose of morphine in patients included in this study was significantly related to variation in UGT2B7 T802C. Age was significantly related to both dose and concentration of morphine in blood. Regression analysis showed that 30% of differences in variation in morphine dose could be explained by SNPs in these genes. The genotype distribution was similar between the forensic cases and the patients. However, the mean concentration of morphine was higher in forensic cases compared to patients. We conclude that gene polymorphisms contribute significantly to the variation in morphine concentrations observed in individual patients. This article is protected by copyright. All rights reserved.
      PubDate: 2014-05-19T06:50:10.927778-05:
      DOI: 10.1111/bcpt.12248
       
  • Reperfusion Therapy with Low‐Dose Insulin or Insulin‐Like
           Growth Factor 2; Myocardial Function and Infarct Size in a Porcine Model
           of Ischaemia and Reperfusion
    • Authors: Pirjo‐Riitta Salminen; Geir Olav Dahle, Christian Arvei Moen, Anita Wergeland, Anne Kristin Jonassen, Rune Haaverstad, Knut Matre, Ketil Grong
      Abstract: In an open‐chest porcine model, we examined whether myocardial pharmacological conditioning at the time of reperfusion with low‐dose insulin or insulin‐like growth factor 2 (IGF2), not affecting serum glucose levels, could reduce infarct size and improve functional recovery. Two groups of anaesthetized pigs with either 60 or 40 min. of left anterior descending artery occlusion (total n=42) were randomized to receive either 0.9% saline‐, insulin‐ or IGF2 infusion for 15 min., starting 5 min. before a 180‐min. reperfusion period. Repeated fluorescent microsphere injections were used to confirm ischaemia and reperfusion. Area at risk and infarct size was determined with Evans Blue and triphenyltetrazolium chloride staining. Local myocardial function was evaluated with multilayer radial tissue Doppler strain and speckle‐tracking strain from epicardial echocardiography. Western blotting and TUNEL staining were performed to explore apoptosis. Infarct size did not differ between treatment groups and was 56.7±6.8%, 49.7 ± 9.6%, 56.2 ± 8.0% of area at risk for control‐, insulin‐ and IGF2 group, respectively, in the 60‐min. occlusion series. Corresponding values were 45.6 ± 6.0%, 48.4 ± 7.2% and 34.1 ± 5.8% after 40‐min. occlusion. Global and local cardiac function did not differ between treatment groups. No differences related to treatment could be found in myocardial tissue‐cleaved caspase‐3 content or the degree of TUNEL staining. Reperfusion therapy with low‐dose insulin or with IGF2 neither reduced infarct size nor improved function in reperfused myocardium in this in vivo porcine model. This article is protected by copyright. All rights reserved.
      PubDate: 2014-05-19T06:47:56.036778-05:
      DOI: 10.1111/bcpt.12255
       
  • Preclinical and Clinical Safety Studies of CMX‐2043: A
           Cytoprotective Lipoic Acid Analogue for Ischaemia‐Reperfusion Injury
           
    • Authors: Steven A. Kates; Alan S. Lader, Ralph Casale, Reinier Beeuwkes
      Abstract: CMX–2043 is an α‐lipoic acid analogue targeted to reduction of cellular injury and organ damage due to ischaemia–reperfusion injury (IRI). It has been shown to be effective in a rat model of cardiac IRI. The studies here reported evaluate its safety and pharmacokinetic profile in preparation for human clinical studies in procedures associated with IRI. Safety and tolerability were tested in standard preclinical in vitro and animal models and in a Phase 1 human clinical trial. CMX‐2043 did not bind to a wide range of receptors and specific targets at approximately 4 g/mL (10 M). It was not mutagenic by Ames assay; did not produce chromosome aberrations in CHO cells and was negative for clastogenic potential. Toxicological studies in rats including both single and 14‐day repeat intravenous doses, and in dogs (single intravenous dose) with a 2‐week recovery period were conducted. The NOAEL in rats and dogs were 30 and >10 mg/kg, respectively. No serious adverse events were reported in a placebo‐controlled, sequential dose escalation Phase 1 clinical trial. The low toxicity in the preclinical studies and absence of adverse events in the Phase 1 trial have supported investigation of CMX‐2043 in a human efficacy trial. This article is protected by copyright. All rights reserved.
      PubDate: 2014-05-16T06:56:08.837701-05:
      DOI: 10.1111/bcpt.12254
       
  • The Neuronal Cytoskeleton as a Potential Target in the Developmental
           Neurotoxicity of Organophosphorothionate Insecticides
    • Authors: John Flaskos
      Abstract: Phosphorothionates are toxicologically the most important class of organophosphorus ester (OP) insecticides. Phosphorothionates are metabolically converted in vivo to their oxon analogues. These oxon metabolites can bind and inhibit acetylcholinesterase, thus causing acute cholinergic neurotoxicity. Oxon binding to the same target may also be partly responsible for manifestation of the ‘intermediate syndrome’. More recent evidence suggests that the oxons may be also capable of inducing developmental neurotoxicity. The neuronal cytoskeleton may represent a potential target for the developmental neurotoxicity of the oxons because of its vital importance in many stages of normal neurodevelopment. Data obtained in the last five years and critically reviewed here indicate that the oxon metabolites, at concentrations that can be attained in vivo, exert potent effects on the neuronal cytoskeleton disrupting all three cytoskeletal networks. This disruption is expressed at the level of cytoskeletal protein expression, intracellular distribution, post translational modification, cytoskeletal dynamics and function and may involve effects on both neuronal and glial cells. These effects are not secondary to other changes but may constitute primary effects of the oxons, as these compounds have been shown to be capable of covalently binding to and organophosphorylating multiple sites on tubulin and actin. Analogous studies must be extended to include other neurodevelopmentally important cytoskeletal proteins, such as NFH, NFM and tau, which are known to contain unusually high numbers of phosphorylatable sites and to establish whether organophosphorylation by the oxons takes place at sites where neurodevelopmentally relevant, endogenous, reversible phosphorylation is known to occur. This article is protected by copyright. All rights reserved.
      PubDate: 2014-05-16T04:07:36.775188-05:
      DOI: 10.1111/bcpt.12204
       
  • EGCG Promotes the Development of Mouse 2‐Cell Embryos In Vitro by
           Regulating Mitochondrial Activity and Expression of Genes Related to p53
           Signalling Pathway
    • Authors: Weiyu Zhang; Junjie Lv, Yanqin Zhang, Yufei Jiang, Chenfeng Chu, Shie Wang
      Abstract: Preliminary studies have found that the epigallocatechin gallate (EGCG) at proper concentration could promote development of pre‐implantation mouse embryos in vitro. However, the underlying mechanisms have not been well understood. In this study, we collected 1‐cell embryos from Kunming (KM) mice, cultured them in M16 medium or M16 medium supplemented with 10 μg/mL EGCG, and investigated the effects of EGCG on mitochondrial activity and reactive oxygen species (ROS) level of 2‐cell embryos. Furthermore, we explored expression differences of genes related to p53 signalling pathway in 2‐cell embryos using a PCR array. The results showed that ROS level and mitochondrial membrane potential were significantly lower in embryos cultured in the EGCG group than in the M16 group (p0.05). PCR array test results showed that 18 genes were differentially expressed, among which 8 genes involving cell growth, cell cycle regulation and mRNA transcription were up‐regulated and 10 genes involving apoptosis, cell cycle arrest and DNA repair were down‐regulated in the EGCG groups. It is concluded that EGCG could promote the development of 1‐cell embryos in vitro possibly due to its ability to scavenge ROS and regulate mitochondrial activity. In addition, EGCG could influence expression of genes related to p53 signalling pathway in 2‐cell embryos and promote cell cycle progression. This article is protected by copyright. All rights reserved.
      PubDate: 2014-05-12T01:09:12.658965-05:
      DOI: 10.1111/bcpt.12252
       
  • Mephedrone, Methylone and 3,4‐Methylenedioxypyrovalerone (MDPV)
           Induce Conditioned Place Preference in Mice
    • Authors: Louise Karlsson; Mikael Andersson, Robert Kronstrand, Fredrik C. Kugelberg
      Abstract: During the last decade, there has been a worldwide increase in popularity and abuse of synthetic cathinones. Common ingredients of the so‐called “bath salts” include mephedrone, methylone and 3,4‐methylenedioxypyrovalerone (MDPV). Relatively little information about the pharmacology and addiction potential of these drugs is available. We used the conditioned place preference (CPP) paradigm to explore the reinforcing effects of three different synthetic cathinones. The primary aim of this study was to investigate whether mephedrone, methylone and MDPV induce CPP in mice. The secondary aims were to investigate a possible dose response CPP and whether the synthetic cathinones induce higher CPP than amphetamine at equal dose. C57BL/6 mice were conditioned to mephedrone, methylone, MDPV and amphetamine at doses of 0.5, 2, 5, 10 or 20 mg/kg (i.p.). During the conditioning, the mice received two training sessions per day for four days. All four tested drugs showed a significant place preference compared to controls. Mice conditioned with MDPV (5 and 10 mg/kg) displayed a greater preference score compared to mice conditioned with amphetamine (5 and 10 mg/kg). Our findings show that mephedrone, methylone and MDPV produce CPP equal or higher than amphetamine strongly suggesting addictive properties. Given the public health concern of abuse, future pharmacological studies are necessary to fully understand the effects of these drugs. This article is protected by copyright. All rights reserved.
      PubDate: 2014-05-06T02:04:43.476062-05:
      DOI: 10.1111/bcpt.12253
       
  • A Nationwide Study of ADHD Drug Use among Adults in Iceland
           2003‐2012
    • Authors: Drifa Palin Geirs; Anton Pottegård, Matthías Halldórsson, Helga Zoëga
      Abstract: In this study, we leveraged on complete nationwide prescription data for the total adult population in Iceland (N=227,000) to examine how attention‐deficit/hyperactivity disorder (ADHD) drugs have been used over the past decade. In particular, we aimed to describe the prevalence, incidence and duration of use of stimulants and atomoxetine, among adults (≥19 years) in Iceland, with regard to sex, age, type of drug and specialty of the prescribing physician. Our results indicate that the 1‐year period prevalence of ADHD drug use rose, from 2.9 to 12.2 per 1,000 adults between 2003 and 2012, with the most pronounced increases among young adults (19‐24 years). The annual incidence increased 3‐fold, similarly among men and women. Extended release methylphenidate formulations were the most commonly used ADHD drugs. Specialists in psychiatry initiated treatment in 79% of new adult ADHD drug users. The proportion of users still receiving treatment after one year varied from 43.0% (19‐24 years), 57.2% (25‐49 years) to 47.5% (50+ years). After 3 years, the corresponding proportions still on treatment were 12.4%, 24.5% and 24.3%, and after 5 years 7.9%, 15.9% and 16.8%. These results of increasing ADHD drug use and short treatment durations call for further investigation of the quality of treatment regimens for adults with ADHD and better follow‐up of patients treated with ADHD drugs. This article is protected by copyright. All rights reserved.
      PubDate: 2014-05-06T02:04:39.675047-05:
      DOI: 10.1111/bcpt.12243
       
  • Professor Folke Sjöqvist is the 2013 BCPT Nordic Prize Winner in
           Basic & Clinical Pharmacology & Toxicology
    • Authors: Kim Brøsen
      Abstract: Professor Folke Sjöqvist who recently turned 80, is still very active and has accomplished remarkable results in many areas of Clinical Pharmacology. He began his thesis work under the pharmacologist‐toxicologist pioneer Professor Bo Holmstedt and with Professor Börje Uvnäs chairing the institution at the Karolinska Institute in Stockholm. The thesis concerned basic experimental pharmacology and ganglionic autonomic transmission. He then had a long postdoc in the USA where his scientific interest was profoundly reoriented towards clinical pharmacology. The most important influence was in the laboratory of the legendary Bernard B. Brodie at the National Institutes of Health (NIH). Professor Sjöqvist became engaged in the new fields of drug metabolism exploring the roles of species and interindividual differences and innovative methods for specific chemical drug analysis. He also studied clinical trial methodology with Professor Louis Lasagna at Johns Hopkins in Baltimore. This article is protected by copyright. All rights reserved.
      PubDate: 2014-05-05T01:14:28.97447-05:0
      DOI: 10.1111/bcpt.12247
       
  • Age‐related Pharmacology
    • Pages: 1 - 4
      PubDate: 2014-06-23T03:40:42.697776-05:
      DOI: 10.1111/bcpt.12259
       
  • Cardiovascular Pharmacology
    • Pages: 5 - 53
      PubDate: 2014-06-23T03:40:43.295997-05:
      DOI: 10.1111/bcpt.12259_1
       
  • Clinical Pharmacology
    • Pages: 54 - 91
      PubDate: 2014-06-23T03:40:41.965505-05:
      DOI: 10.1111/bcpt.12259_2
       
  • Drug Discovery and Development
    • Pages: 92 - 161
      PubDate: 2014-06-23T03:40:41.83942-05:0
      DOI: 10.1111/bcpt.12259_3
       
  • Drug Metabolism and Disposition
    • Pages: 162 - 172
      PubDate: 2014-06-23T03:40:42.573352-05:
      DOI: 10.1111/bcpt.12259_4
       
  • Drugs and the Brain
    • Pages: 173 - 222
      PubDate: 2014-06-23T03:40:42.473619-05:
      DOI: 10.1111/bcpt.12259_5
       
  • Drugs for Infectious Disease
    • Pages: 223 - 235
      PubDate: 2014-06-23T03:40:42.649662-05:
      DOI: 10.1111/bcpt.12259_6
       
  • Endocrine Pharmacology
    • Pages: 236 - 249
      PubDate: 2014-06-23T03:40:43.328308-05:
      DOI: 10.1111/bcpt.12259_7
       
  • Fundamental Pharmacological Mechanisms
    • Pages: 250 - 284
      PubDate: 2014-06-23T03:40:42.959555-05:
      DOI: 10.1111/bcpt.12259_8
       
  • Immunopharmacology
    • Pages: 285 - 302
      PubDate: 2014-06-23T03:40:41.932489-05:
      DOI: 10.1111/bcpt.12259_9
       
  • Oncology
    • Pages: 303 - 318
      PubDate: 2014-06-23T03:40:42.521379-05:
      DOI: 10.1111/bcpt.12259_10
       
  • Pharmacology and Technology
    • Pages: 319 - 325
      PubDate: 2014-06-23T03:40:41.870134-05:
      DOI: 10.1111/bcpt.12259_11
       
  • Pharmacology Education
    • Pages: 326 - 333
      PubDate: 2014-06-23T03:40:42.786691-05:
      DOI: 10.1111/bcpt.12259_12
       
  • Regulatory Affairs & Management
    • Pages: 334 - 338
      PubDate: 2014-06-23T03:40:43.024328-05:
      DOI: 10.1111/bcpt.12259_13
       
  • Specialised Systems Pharmacology
    • Pages: 339 - 349
      PubDate: 2014-06-23T03:40:41.89941-05:0
      DOI: 10.1111/bcpt.12259_14
       
  • Toxicology
    • Pages: 350 - 369
      PubDate: 2014-06-23T03:40:41.714875-05:
      DOI: 10.1111/bcpt.12259_15
       
  • Veterinary Pharmacology
    • Pages: 370 - 374
      PubDate: 2014-06-23T03:40:41.807692-05:
      DOI: 10.1111/bcpt.12259_16
       
  • Author Index
    • Pages: 375 - 402
      PubDate: 2014-06-23T03:40:41.999238-05:
      DOI: 10.1111/bcpt.12258
       
 
 
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