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Drug combination

Eric Seiti Yamanaka, Luis A Tortajada-Genaro, Nuria Pastor, Ángel Maquieira
The genotyping of a single-nucleotide polymorphism (SNP) is addressed through methods based on loop-mediated isothermal amplification (LAMP) combined with user-friendly optical read-outs to cover the current demand for point-of-care DNA biomarker detection. The modification of primer design and reaction composition improved the assay selectivity yielding allele-specific results and reducing false-positive frequency. Furthermore, the reduced cost, ease of use and effectiveness of colorimetric detection (solution and hybridisation chip formats) were availed for the image capture by a smartphone, reching high sensitivity...
March 8, 2018: Biosensors & Bioelectronics
Viviana Izzo, Bruno Charlier, Elena Bloise, Marine Pingeon, Marianna Romano, Antonietta Finelli, Alfonso Vietri, Valeria Conti, Valentina Manzo, Maria Alfieri, Amelia Filippelli, Fabrizio Dal Piaz
Exposure of healthcare workers to anticancer drugs requires the combined action of environmental and biological monitoring to assess the effective level of exposure to these chemicals, to improve awareness and to avoid adverse health effects on this category of workers. Cancer chemotherapeutic drugs show different mechanisms of action due to diverse chemical structures; consequently, they differ in hydrophobicity, pharmacokinetics and pharmacodynamics. Therefore, the appearance, accumulation and elimination of each of these molecules in body fluids and tissues might be extremely variable; this prompts the need for a rapid and versatile analytical protocol for the biological monitoring of possible exposure of workers involved in the manipulation, administration and disposal of cancer chemotherapeutic drugs...
March 13, 2018: Journal of Pharmaceutical and Biomedical Analysis
Karin Kfir-Elirachman, Rona Ortenberg, Bella Vizel, Michal J Besser, Iris Barshack, Jacob Schachter, Yael Nemlich, Gal Markel
BRAF becomes constitutively activated in 50% to 70% of melanoma cases. CEACAM1 has a dual role in melanoma, including facilitation of cell proliferation and suppression of infiltrating lymphocytes, which are consistent with its value as a marker for poor prognosis in melanoma patients. Here we show that BRAFV600E melanoma cells treated with BRAF and MEK inhibitors (MAPKi) downregulate CEACAM1 mRNA and protein expression in a dose- and exposure time-dependent manners. Indeed, there is a significant correlation between the presence of BRAFV600E and CEACAM1 expression in melanoma specimens obtained from 45 patients...
March 17, 2018: Neoplasia: An International Journal for Oncology Research
Zsolt Zador, Andrew T King, Nophar Geifman
BACKGROUND: Atypical meningiomas are common central nervous system neoplasms with high recurrence rate and poorer prognosis compared to their grade I counterparts. Surgical excision and radiotherapy remains the mainstay therapy but medical treatments are limited. We explore new drug candidates using computational drug repurposing based on the gene expression signature of atypical meningioma tissue with subsequent analysis of drug-generated expression profiles. We further explore possible mechanisms of action for the identified drug candidates using ingenuity pathway analysis (IPA)...
2018: PloS One
Klaus Rose, Jane M Grant-Kels
Importance-Pediatric melanoma occurs, albeit rarely. Should patients be treated by today's medical standards, or be subjected to medically unnecessary clinical studies? Observations-We identified international, industry-sponsored pediatric melanoma studies triggered by regulatory demands in and further pediatric melanoma studies demanded by European Union pediatric investigation plans. We retrieved related regulatory documents from the internet. We analyzed these studies for rationale and medical beneficence on the basis of physiology, pediatric clinical pharmacology and rationale...
March 20, 2018: Children
Karen Batschinski, Nikolaos Dervisis, Barbara Kitchell, Rebecca Newman, Todd Erfourth
A retrospective study was performed to evaluate response rate, time to progression, and toxicity of a bleomycin and cytosine arabinoside (Bleo/Cytarabine) combination protocol for dogs with relapsed lymphoma (LSA). Dogs diagnosed with LSA and previously treated with chemotherapy were included in the study. A total of 20 dogs met the inclusion criteria, and 19 were evaluable for response. Bleomycin was administered subcutaneously on days 1 and 8 and cytosine arabinoside was administered subcutaneously on days 1-5 of a 21-day cycle...
March 20, 2018: Journal of the American Animal Hospital Association
Andrew J Clulow, Malinda Salim, Adrian Hawley, Elliot P Gilbert, Ben Boyd
Efforts to develop orally-administered drugs tend to place an exceptional focus on aqueous solubility as this is an essential criterion for their absorption in the gastro-intestinal tract. In this work we examine the solid state behaviour and solubility of OZ439, a promising single-dose cure for malaria being developed as the highly water-soluble mesylate salt. The aqueous phase behaviour of the OZ439 mesylate salt was determined using a combination of small angle neutron and X-ray scattering (SANS and SAXS, respectively)...
March 20, 2018: Molecular Pharmaceutics
Agnieszka J Nawrat-Szołtysik, Anna Polak, Andrzej Małecki, Laura Piejko, Dominika Grzybowska-Ganszczyk, Michał Kręcichwost, Józef Opara
BACKGROUND: Osteoporosis is one of the most common diseases that develop with age and cause high morbidity and mortality among elderly people. OBJECTIVES: This study was set out to evaluate the influence of a program of modified Sinaki exercises, Nordic walking (NW) and a combination of these physical activities on people with osteoporosis. MATERIAL AND METHODS: A sample consisting of 91 women aged 65-98 years living in residential care facilities was randomized into 4 groups...
March 20, 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
Nazanin Abolhassani, Julien Castioni, Valérie Santschi, Gérard Waeber, Pedro Marques-Vidal
BACKGROUND: Polypharmacy (PP) and excessive polypharmacy (EPP) are increasingly common and associated with risk of drug-drug interactions (DDIs). We aimed to measure the trends and determinants of PP and DDIs among patients discharged from the Department of Internal Medicine of the Lausanne University Hospital. METHODS: The retrospective study included 17,742 adult patients discharged between 2009 and 2015. Polypharmacy and EPP were defined as the concomitant prescription of five or more and ten or more drugs, respectively...
March 19, 2018: Journal of Patient Safety
Mariana V Meireles, Ana Roberta P Pascom, Elisabeth C Duarte
OBJECTIVE: To identify clinical, sociodemographic and treatment-related factors associated with early virological response in HIV-infected adults starting antiretroviral treatment (ART) in Brazil in 2014-2015. METHODS: Data from four information systems from the Brazilian AIDS Program were combined to create a historical cohort. Unconditional logistic regression models were used to assess the likelihood of not achieving virological suppression (VLS), defined as having either a viral load count (VL) >200 copies/mL or an aids-related death recorded within 180±90 days after treatment initiation...
March 19, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Talia Serseg, Khedidja Benarous
Side effects of some drugs may be useful in certain cases. In this work, we studied the inhibitory effects of some medications as: Folic Acid which is taken by pregnant women, Colchicine and Febuxostat which is used as treatment of gout disease. These cases are linked to obesity, where women (BMI ≥ 30) have twice higher odds of having an NTD-affected pregnancy than the normal weight women, and the Gout disease frequently occurs in combination of a Metabolic syndrome. The risk of gout increases with the increase of the mass index...
March 18, 2018: Endocrine, Metabolic & Immune Disorders Drug Targets
Xue Han, Xiao Kuang, Zhenjie Wang, Xinyu Wang, Hongzhuo Liu
BACKGROUND: Hydroxyapatite(HA) was emerging as the most promising biomaterial owing to its excellent bioactivity, biocompatibility, and high compressive strength for segmental bone defects. However, due to the lack of synergistic signals of osteogenic cells or growth factors, attempts concerning HA have not achieved ideal therapeutical effect. OBJECTIVE: This work was intended to combine HA particles with nerve growth factor (NGF) to co-accelerate the bone repair...
March 19, 2018: Current Drug Delivery
Peddi Maharshi, Sachin Kumar Singh, Monica Gulati, Ankit Kumar Yadav, Varun Garg, Bimlesh Kumari, K Gowthamarajan
A major challenge in targeting orally administered drugs to colon is their passage through the long gastrointestinal path comprising highly variant conditions in terms of pH, viscosity, gut motility and microbial flora. Approaches of pH controlled release and microbially triggered release have proved to be successful in achieving colon targeting only to a partial extent. In an attempt to improve targeting, both these approaches have been combined together with the approach of liquisolid technology which, hitherto, remains unexplored for colon targeting...
March 19, 2018: Current Drug Delivery
Delia De Lisi, Ugo De Giorgi, Cristian Lolli, Giuseppe Schepisi, Vincenza Conteduca, Cecilia Menna, Giuseppe Tonini, Daniele Santini, Alberto Farolfi
To date, results of combination therapy studies have shown no meaningful clinical benefit over monotherapy and an unacceptably high degree of toxicity in the treatment of metastatic renal cell carcinoma (RCC), with the exception of a combination of immune-checkpoint inhibitors and the association of lenvatinib with everolimus. Lenvatinib is a potent multi-targeted tyrosine kinase inhibitor that targets VEGFR pathways. Everolimus inhibits primarily mTORC1 complex, a downstream effecter of the intracellular PI3K/AKT/mTOR pathway...
March 20, 2018: Expert Opinion on Drug Metabolism & Toxicology
Laura Pogliani, Sara Baldelli, Dario Cattaneo, Paola Pileri, Emilio Clementi, Irene Cetin, M D Gianvincenzo Zuccotti
OBJECTIVE: Selective serotonin reuptake inhibitors are commonly used for the treatment of pregnancy-related and postnatal depression. However, only a few studies have evaluated the passage of these drugs into human milk, often with conflicting results. Here, we sought to evaluate the passage of selective serotonin reuptake inhibitors into human milk in the first days after delivery and their potential association with neonatal outcomes. STUDY DESIGN: The passage of selective serotonin reuptake inhibitors into human milk was expressed both as percentage of milk-to-plasma ratio of drug concentrations and as the relative infant dose...
March 20, 2018: Journal of Maternal-fetal & Neonatal Medicine
Miran Brvar, Ming Yin Chan, Andrew H Dawson, Richard R Ribchester, Michael Eddleston
INTRODUCTION: Treatment of acute organophosphorus or carbamate insecticide self-poisoning is often ineffective, with tens of thousands of deaths occurring every year. Researchers have recommended the addition of magnesium sulfate or calcium channel blocking drugs to standard care to reduce acetylcholine release at cholinergic synapses. OBJECTIVE: We aimed to review systematically the evidence from preclinical studies in animals exposed to organophosphorus or carbamate insecticides concerning the efficacy of magnesium sulfate and calcium channel blocking drugs as therapy compared with placebo in reducing mortality or clinical features of poisoning...
March 20, 2018: Clinical Toxicology
Erin E Burke, Jonathan S Zager
Introduction Current treatment of advanced melanoma is rapidly changing with the introduction of new and effective therapies including systemic as well as locoregional therapies. An example of one such locoregional therapy is intralesional injection with talimogene laherparepvec (T-VEC). Areas Covered T-VEC has been shown in a number of studies to be an effective treatment for patients with stage IIIB, IIIC and IVM1a melanoma. In this article the effectiveness, pharmacokinetics and safety profile of TVEC is reviewed...
March 20, 2018: Expert Opinion on Drug Metabolism & Toxicology
Maria-Eleni Kyriazi, Davide Giust, Afaf H El-Sagheer, Peter M Lackie, Otto L Muskens, Tom Brown, Antonios G Kanaras
The design of nanoparticulate systems which can perform multiple synergistic functions in cells with high specificity and selectivity is of great importance in applications. Here we combine recent advances in DNA-gold nanoparticle self-assembly and sensing to develop gold nanoparticle dimers that are able to perform multiplexed synergistic functions within a cellular environment. These dimers can sense two mRNA targets and simultaneously or independently deliver one or two DNA-intercalating anticancer drugs (doxorubicin and mitoxantrone) in live cells...
March 20, 2018: ACS Nano
Tony K L Kiang
Elbasvir and grazoprevir, in a fixed-dose combination of 50 and 100 mg, respectively, have received approval to be administered orally once daily, with or without ribavirin, for the treatment of chronic hepatitis C virus (HCV) infections. The absorption characteristics of elbasvir and grazoprevir have been adequately summarized, although differences were observed for grazoprevir (e.g., increased exposure at steady state in patients), but not elbasvir, between healthy and HCV-infected subjects. Inconsistencies with respect to absorption were also reported on the effects of food or acid reducers (famotidine or pantoprazole) in the literature...
March 20, 2018: European Journal of Drug Metabolism and Pharmacokinetics
James D Weinstein
Despite decades of research, at present there is no curative therapy for Alzheimer's disease. Changes in the way new drugs are tested appear to be necessary. Three changes are presented here and will be discussed. The first change is that Alzheimer's disease must be considered a disease of four major pathological processes, not one. The four processes are: 1) vascular hypoperfusion of the brain with associated mitochondrial dysfunction, 2) destructive protein inclusions, 3) uncontrolled oxidative stress, and 4) proinflammatory immune processes secondary to microglial and astrocytic dysfunction in the brain...
February 2018: Neural Regeneration Research
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