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Drug synergy

Massimo Nabissi, Maria Beatrice Morelli, Massimo Offidani, Consuelo Amantini, Silvia Gentili, Alessandra Soriani, Claudio Cardinali, Pietro Leoni, Giorgio Santoni
Several studies showed a potential anti-tumor role for cannabinoids, by modulating cell signaling pathways involved in cancer cell proliferation, chemo-resistance and migration. Cannabidiol (CBD) was previously noted in multiple myeloma (MM), both alone and in synergy with the proteasome inhibitor bortezomib, to induce cell death. In other type of human cancers, the combination of CBD with Δ9-tetrahydrocannabinol (THC) was found to act synergistically with other chemotherapeutic drugs suggesting their use in combination therapy...
October 18, 2016: Oncotarget
Juan Rosas-Guzmán, Juan Rosas-Saucedo, Alma R J Romero-García
Type 2 Diabetes Mellitus (T2DM) is a chronic illness with high prevalence in Mexico, Latin-America, and the world and is associated to high morbidity, disability, and mortality rate, especially in developing countries. T2DM physiopathology is very complex; insulin resistance in the muscle, liver, and adipose tissue, a reduction in the production of incretins (mainly GLP-1) in the intestine, increased glucagon synthesis, an insufficient response of insulin generation, and increased glucose reabsorption in the kidney lead all together to an hyperglycemic state, which has been closely associated with the development of micro and macrovascular complications...
August 29, 2016: Reviews on Recent Clinical Trials
Grzegorz Fila, Anna Kawiak, Mariusz Grinholc
Pseudomonas aeruginosa is among the most common pathogens responsible for both acute and chronic infections of high incidence and severity. Additionally, P. aeruginosa resistance to conventional antimicrobials has increased rapidly over the past decade. Therefore, it is crucial to explore new therapeutic options, particularly options that specifically target the pathogenic mechanisms of this microbe. The ability of a pathogenic bacterium to cause disease is dependent upon the production of agents termed 'virulence factors', and approaches to mitigate these agents have gained increasing attention as new antibacterial strategies...
October 20, 2016: Virulence
Gemma L Buckland Merrett, Gerald Bloom, Annie Wilkinson, Hayley MacGregor
The emergence and spread of antibiotic resistant pathogens poses a big challenge to policy-makers, who need to oversee the transformation of health systems that evolved to provide easy access to these drugs into ones that encourage appropriate use of antimicrobials, whilst reducing the risk of resistance. This is a particular challenge for low and middle-income countries with pluralistic health systems where antibiotics are available in a number of different markets. This review paper considers access and use of antibiotics in these countries from a complex adaptive system perspective...
2016: Journal of Pharmaceutical Policy and Practice
Wan Harun Himratul-Aznita, Che Omran Nor-Zulaila, Khairuddin Nurul-Fatihah
Candida spp. is the most prevalent species causing systemic fungal infections. The effect of antifungal agents were screened in vitro and their synergism effect were determined between hydroxychavicol (HC) in association with commercialized antifungal drugs-amphotericin B (AMB), and 5-fluorocytosine (5-FC) alone and in combination against five different oral Candida spp. in their planktonic states at different ratio (1:1 v/v; 1:2 v/v and 2:1 v/v). In vitro susceptibilities of Candida spp. to HC and commercialized antifungal agents were investigated by broth microdilution method as described by Clinical and Laboratory Standards Institute M38-A2...
2016: SpringerPlus
Sanmuga Priya Ekambaram, Senthamil Selvan Perumal, Ajay Balakrishnan, Nathiya Marappan, Sabari Srinivasan Gajendran, Vinodhini Viswanathan
AIM/BACKGROUND: Medicinal plants have ability to resist microorganisms by synthesizing secondary metabolites such as phenols. Rosmarinic acid (RA) is a phenylpropanoid widely distributed in plants and well known as therapeutic and cosmetic agent. Methicillin-resistant Staphylococcus aureus (MRSA) which is resistant to all kinds of β-lactams, threatens even most potent antibiotics. To improve the efficiency of antibiotics against multi-drug resistant bacteria and to reduce the antibiotic dose, the antibacterial activity and the synergistic effect of RA with standard antibiotics against S...
September 2016: Journal of Intercultural Ethnopharmacology
N R Datta, S Krishnan, D E Speiser, E Neufeld, N Kuster, S Bodis, H Hofmann
Effective multimodal cancer management requires the optimal integration of diagnostic and therapeutic modalities. Radiation therapy, chemotherapy and immunotherapy, alone or in combination, are integral parts of various cancer treatment protocols. Hyperthermia at 39-45°C is a potent radiosensitiser and has been shown to improve therapeutic outcomes in various tumours through its synergy with chemotherapy. Gene silencing approaches, using small interfering RNAs and microRNAs, are also being explored in clinical trials in oncology...
October 3, 2016: Cancer Treatment Reviews
Alan Eastman
The high failure rate of anticancer drug discovery and development has consumed billions of dollars annually. While many explanations have been provided, I believe that misinformation arising from inappropriate cell-based screens has been completely over-looked. Most cell culture experiments are irrelevant to how drugs are subsequently administered to patients. Usually, drug development focuses on growth inhibition rather than cell killing. Drugs are selected based on continuous incubation of cells, then frequently administered to the patient as a bolus...
October 14, 2016: Oncotarget
Keelara Shivalingaiah Savitha, Radhika Dhanpal, J Shilpa
BACKGROUND: Multimodal analgesia (MMA) by synergy with volatile anesthetics minimizes their use thus decreasing operation theater pollution and greenhouse gas emission. AIMS: To estimate minimum alveolar concentration (MAC) requirement of isoflurane (ISO) for skin incision with use of MMA in the study group versus conventional regime in the control group for a constant bispectral index (BIS). To observe the side effects of analgesic drugs administered in the study...
September 2016: Anesthesia, Essays and Researches
Devyani Deshpande, Shashikant Srivastava, Eric Nuermberger, Jotam G Pasipanodya, Soumya Swaminathan, Tawanda Gumbo
BACKGROUND:  No treatment regimens have been specifically designed for children, in whom tuberculosis is predominantly intracellular. Given their activity as monotherapy and their ability to penetrate many diseased anatomic sites that characterize disseminated tuberculosis, linezolid and moxifloxacin could be combined to form a regimen for this need. METHODS:  We examined microbial kill of intracellular Mycobacterium tuberculosis (Mtb) by the combination of linezolid and moxifloxacin multiple exposures in a 7-by-7 mathematical matrix...
November 1, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Shashikant Srivastava, Devyani Deshpande, Jotam G Pasipanodya, Tania Thomas, Soumya Swaminathan, Eric Nuermberger, Tawanda Gumbo
Children with tuberculosis are treated with drug regimens copied from adults despite significant differences in antibiotic pharmacokinetics, pathology, and the microbial burden between childhood and adult tuberculosis. We sought to develop a new and effective oral treatment regimen specific to children of different ages. We investigated and validated the concept that target drug concentrations associated with therapy failure and death in children are different from those of adults. On that basis, we proposed a 4-step program to rapidly develop treatment regimens for children...
November 1, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Mark A Strom, Girish C Mohan, Peter A Lio
Dermatologists frequently employ combination therapy to treat various diseases, but the evidence to support the use of such combinations is often lacking. Synergy is an appealing although somewhat ambiguous concept in medicine. Utilizing synergy allows clinicians to provide the most efficacious combination of treatments to patients, while potentially minimizing adverse effects and reducing the development of drug resistance. Definitions of synergy vary, but ultimately converge on finding a therapeutic advantage in combining treatments...
October 1, 2016: Journal of Drugs in Dermatology: JDD
Behnam Behinaein, Karen Rudie, Waheed Sangrar
Epidermal Growth Factor Receptor (EGFR) signaling to the Ras-MAPK pathway is implicated in the development and progression of cancer and is a major focus of targeted combination therapies. Physiochemical models have been used for identifying and testing the signal-inhibiting potential of targeted therapies, however, their application to larger multi-pathway networks is limited by the availability of experimentally-determined rate and concentration parameters. An alternate strategy for identifying and evaluating drug-targetable nodes is proposed...
October 3, 2016: IEEE/ACM Transactions on Computational Biology and Bioinformatics
Pauline D Scanlan, Anna M Bischofberger, Alex R Hall
Although experiments indicate that the abiotic environment plays an important role in bacterial interactions with their parasitic viruses (bacteriophages or phages), it is not yet clear how exposure to compounds present in nature alters the impact of phages on bacterial growth and evolution. To address this question we exposed Escherichia coli K12 MG1655, in combination with three lytic phages, to various substances that natural and clinical microbial populations are likely to encounter: bile salts (present in mammalian gastrointestinal tracts), sodium dodecyl sulfate (SDS, a common surfactant in cleaning and hygiene products), and four antibiotics (present at variable concentrations in natural and clinical environments)...
October 12, 2016: FEMS Microbiology Ecology
Paulina Koczurkiewicz, Ewa Kowolik, Irma Podolak, Dawid Wnuk, Kamil Piska, Anna Łabędź-Masłowska, Katarzyna Wójcik-Pszczoła, Elżbieta Pękala, Jarosław Czyż, Marta Michalik
Triterpene saponins are secondary metabolites typical for higher plants. They possess a wide range of pharmaceutical and biological activities. These include anti-inflammatory, vasoprotective, expectorant, and antitumor properties. In particular, the ability of saponins to enhance the cytotoxicity of chemotherapeutic drugs has opened new perspectives for their application in combined cancer chemotherapy. In this study, the biological activity of the saponin fraction isolated from Lysimachia ciliata (denoted as CIL-1/2) was evaluated to assess its chemosensitizing activity in prostate cancer cell lines (DU-145, PC-3)...
October 13, 2016: Planta Medica
Lori S Hart, JulieAnn Rader, Pichai Raman, Vandana Batra, Michael R Russell, Matthew Tsang, Maria Gagliardi, Lucy Chen, Daniel Martinez, Yimei Li, Andrew Wood, Sunkyu Kim, Sudha Parasuraman, Scott Delach, Kristina A Cole, Shiva Krupa, Markus Boehm, Malte Peters, Giordano Caponigro, John M Maris
PURPOSE: Neuroblastoma is treated with aggressive multi-modal therapy, yet more than 50% of patients experience relapse. We recently showed that relapsed neuroblastomas frequently harbor mutations leading to hyperactivated ERK signaling and sensitivity to MEK inhibition therapy. Here we sought to define a synergistic therapeutic partner to potentiate MEK inhibition. EXPERIMENTAL DESIGN: We first surveyed 22 genetically annotated human neuroblastoma-derived cell lines (from 20 unique patients) for sensitivity to the MEK inhibitor binimetinib...
October 11, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Verónica Seguel, Lorena Castro, Chantal Reigada, Leonel Cortes, María V Díaz, Mariana R Miranda, Claudio A Pereira, Michel Lapier, Carolina Campos-Estrada, Antonio Morello, Ulrike Kemmerling, Juan D Maya, Rodrigo López-Muñoz
Benznidazole is the first-line drug used in treating Chagas disease, which is caused by the parasite Trypanosoma cruzi (T. cruzi). However, benznidazole has limited efficacy and several adverse reactions. Pentamidine is an antiprotozoal drug used in the treatment of leishmaniasis and African trypanosomiasis. In T. cruzi, pentamidine blocks the transport of putrescine, a precursor of trypanothione, which constitutes an essential molecule in the resistance of T. cruzi to benznidazole. In the present study, we describe the effect of the combination of benznidazole and pentamidine on isolated parasites, mammalian cells and in mice infected with T...
October 8, 2016: Experimental Parasitology
Cristina Rostkowska, Caroline M Mota, Taísa C Oliveira, Fernanda M Santiago, Lilian A Oliveira, Gaspar H Korndörfer, Regina M Q Lana, Monica L Rossi, Neusa L Nogueira, Xavier Simonnet, Tiago W P Mineo, Deise A O Silva, José R Mineo
Artemisia annua is used as a source of artemisinin, a potent therapeutic agent used for the treatment of infectious diseases, chiefly malaria. However, the low concentration (from 0.01 to 1.4% of dried leaf matter) of artemisinin in the plant obtained with the traditional cropping system makes it a relatively expensive drug, especially in developing countries. Considering that artemisinin and silicon (Si) are both stored in A. annua glandular trichomes, and that Si accumulation has never been investigated, this study aimed to look into Si effects on A...
2016: Frontiers in Plant Science
Lisa M Greene, Seema M Nathwani, Daniela M Zisterer
T-cell acute lymphoblastic leukemia (T-ALL) is a rare and aggressive hematopoietic malignancy prone to relapse and drug resistance. Half of all T-ALL patients exhibit mutations in Notch1, which leads to aberrant Notch1 associated signaling cascades. Notch1 activation is mediated by the γ-secretase cleavage of the Notch1 receptor into the active intracellular domain of Notch1 (NCID). Clinical trials of γ-secretase small molecule inhibitors (GSIs) as single agents for the treatment of T-ALL have been unsuccessful...
October 2016: Oncology Letters
Ethan B Russo
This overview covers a wide range of cannabis topics, initially examining issues in dispensaries and self-administration, plus regulatory requirements for production of cannabis-based medicines, particularly the Food and Drug Administration "Botanical Guidance." The remainder pertains to various cannabis controversies that certainly require closer examination if the scientific, consumer, and governmental stakeholders are ever to reach consensus on safety issues, specifically: whether botanical cannabis displays herbal synergy of its components, pharmacokinetics of cannabis and dose titration, whether cannabis medicines produce cyclo-oxygenase inhibition, cannabis-drug interactions, and cytochrome P450 issues, whether cannabis randomized clinical trials are properly blinded, combatting the placebo effect in those trials via new approaches, the drug abuse liability (DAL) of cannabis-based medicines and their regulatory scheduling, their effects on cognitive function and psychiatric sequelae, immunological effects, cannabis and driving safety, youth usage, issues related to cannabis smoking and vaporization, cannabis concentrates and vape-pens, and laboratory analysis for contamination with bacteria and heavy metals...
2016: Frontiers in Pharmacology
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