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Morten Baltzer Houlind, Kristian Kjær Petersen, Henrik Palm, Lillian Mørch Jørgensen, Mia Aakjær, Lona Louring Christrup, Janne Petersen, Ove Andersen, Charlotte Treldal
Many analgesics and their metabolites are renally excreted. The widely used Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)-estimated glomerular filtration rate (eGFR) equations are not developed for use in the elderly, while the recent Berlin Initiative Study (BIS), Full Age Spectrum (FAS), and Lund-Malmö revised (LMR) equations are. This observational study investigated differences between creatinine-based eGFR equations and how the choice of equation influences dosage of analgesics in elderly (≥70 years) patients admitted with acute hip fracture...
September 18, 2018: Pharmaceuticals
Veronica Fiorito, Deborah Chiabrando, Emanuela Tolosano
Mitochondrial dysfunction has achieved an increasing interest in the field of neurodegeneration as a pathological hallmark for different disorders. The impact of mitochondria is related to a variety of mechanisms and several of them can co-exist in the same disease. The central role of mitochondria in neurodegenerative disorders has stimulated studies intended to implement therapeutic protocols based on the targeting of the distinct mitochondrial processes. The review summarizes the most relevant mechanisms by which mitochondria contribute to neurodegeneration, encompassing therapeutic approaches...
September 18, 2018: Pharmaceuticals
Dario Ruiz Ciancio, Mauricio R Vargas, William H Thiel, Martin A Bruno, Paloma H Giangrande, María Belén Mestre
Cancer is the second leading cause of death worldwide. Researchers have been working hard on investigating not only improved therapeutics but also on early detection methods, both critical to increasing treatment efficacy, and developing methods for disease prevention. The use of nucleic acids, or aptamers, has emerged as more specific and accurate cancer diagnostic and therapeutic tools. Aptamers are single-stranded DNA or RNA molecules that recognize specific targets based on unique three-dimensional conformations...
September 11, 2018: Pharmaceuticals
Eka Ginanjar, Lilik Indrawati, Iswari Setianingsih, Djumhana Atmakusumah, Alida Harahap, Ina S Timan, Joannes J M Marx
Plasma non-transferrin-bound iron (NTBI) is potentially harmful due to the generation of free radicals that cause tissue damage in vascular and other diseases. Studies in iron-replete and iron-deficient subjects, receiving a single oral test dose of Fe(II)SO₄ or NaFe(III)EDTA with water, revealed that FeSO₄ was well absorbed when compared with NaFeEDTA, while only the Fe(II) compound showed a remarkable increase of NTBI. As NaFeEDTA is successfully used for food fortification, a double-blind randomized cross-over trial was conducted in 11 healthy women with uncomplicated iron deficiency...
September 10, 2018: Pharmaceuticals
Ana Cordeiro Gomes, Ana C Moreira, Gonçalo Mesquita, Maria Salomé Gomes
Iron is an essential nutrient for almost all living organisms, but is not easily made available. Hosts and pathogens engage in a fight for the metal during an infection, leading to major alterations in the host's iron metabolism. Important pathological consequences can emerge from the mentioned interaction, including anemia. Several recent reports have highlighted the alterations in iron metabolism caused by different types of infection, and several possible therapeutic strategies emerge, based on the targeting of the host's iron metabolism...
September 1, 2018: Pharmaceuticals
Adrienne Müller Herde, Silvan D Boss, Yingfang He, Roger Schibli, Linjing Mu, Simon M Ametamey
Several studies showed that [11 C]ABP688 binding is altered following drug-induced perturbation of glutamate levels in brains of humans, non-human primates and rats. We evaluated whether the fluorinated derivative [18 F]PSS232 can be used to assess metabotropic glutamate receptor 5 (mGluR5) availability in rats after pharmacological challenge with ketamine, known to increase glutamate, or ceftriaxone, known to decrease glutamate. In vitro autoradiography was performed on rat brain slices with [18 F]PSS232 to prove direct competition of the drugs for mGluR5...
August 29, 2018: Pharmaceuticals
Sunil Bhandari, Dora I A Pereira, Helen F Chappell, Hal Drakesmith
Iron is an essential trace mineral necessary for life, and iron deficiency anaemia (IDA) is one of the most common haematological problems worldwide, affecting a sixth of the global population. Principally linked to poverty, malnutrition and infection in developing countries, in Western countries the pathophysiology of IDA is primarily linked to blood loss, malabsorption and chronic disease. Oral iron replacement therapy is a simple, inexpensive treatment, but is limited by gastrointestinal side effects that are not inconsequential to some patients and are of minimal efficacy in others...
August 27, 2018: Pharmaceuticals
Aymeric Ousset, Rosanna Chirico, Florent Robin, Martin Alexander Schubert, Pascal Somville, Kalliopi Dodou
This work describes a novel screening strategy that implements small-scale spray-drying in early development of binary amorphous solid dispersions (ASDs). The proposed methodology consists of a three-stage decision protocol in which small batches (20⁻100 mg) of spray-dried solid dispersions (SDSDs) are evaluated in terms of drug⁻polymer miscibility, physical stability and dissolution performance in bio-predictive conditions. The objectives are to select the adequate carrier and drug-loading (DL) for the manufacturing of robust SDSD; and the appropriate stabilizer dissolved in the liquid vehicle of SDSD suspensions, which constitutes the common dosage form used during non-clinical studies...
August 27, 2018: Pharmaceuticals
Micaela Belleperche, Maria C DeRosa
Aptamer binding has been used effectively for diagnostics, in-vivo targeting of therapeutics, and the construction and control of nanomachines. Nanostructures that respond to pH by releasing or changing affinity to a target have also been used for in vivo delivery, and in the construction of sensors and re-usable nanomachines. There are many applications that use aptamers together with pH-responsive materials, notably the targeted delivery of chemotherapeutics. However, the number of reported applications that directly use pH to control aptamer binding is small...
August 26, 2018: Pharmaceuticals
Silvia Catuogno, Carla Lucia Esposito, Paola Ungaro, Vittorio de Franciscis
Epigenetic mechanisms include DNA methylation, posttranslational modifications of histones, chromatin remodeling factors, and post transcriptional gene regulation by noncoding RNAs. All together, these processes regulate gene expression by changing chromatin organization and DNA accessibility. Targeting enzymatic regulators responsible for DNA and chromatin modifications hold promise for modulating the transcriptional regulation of genes that are involved in cancer, as well as in chronic noncommunicable metabolic diseases like obesity, diabetes, and cardiovascular diseases...
August 24, 2018: Pharmaceuticals
Rafael Sebastián Fort, Juan M Trinidad Barnech, Juliette Dourron, Marcos Colazzo, Francisco J Aguirre-Crespo, María Ana Duhagon, Guzmán Álvarez
Prostate cancer is the most common cancer in men around the world. It is a complex and heterogeneous disease in which androgens and their receptors play a crucial role in the progression and development. The current treatment for prostate cancer is a combination of surgery, hormone therapy, radiation and chemotherapy. Therapeutic agents commonly used in the clinic include steroidal and non-steroidal anti-androgens, such as cyproterone acetate, bicalutamide and enzalutamide. These few agents have multiple adverse effects and are not 100% effective...
August 14, 2018: Pharmaceuticals
Tetiana Marchyshak, Tetiana Yakovenko, Igor Shmarakov, Zenoviy Tkachuk
This study investigated the potential hepatoprotective effect of oligoribonucleotides-d-mannitol complexes (ORNs-d-M) against thioacetamide (TAA)-induced hepatotoxicity in mice. The hepatoprotective activity of ORNs-d-M was evaluated in thioacetamide (TAA)-treated C57BL/6J. Results indicate that treatment with ORNs-d-M displayed a protective effect at the TAA-induced liver injury. Treatment with ORNs-d-M, starting at 0 h after the administration of TAA, decreased TAA-elevated serum alanine aminotransferase (ALT) and γ-glutamyl transpeptidase (GGT)...
August 6, 2018: Pharmaceuticals
Klebson S Santos, Andriele M Barbosa, Victor Freitas, Ana Veruska C S Muniz, Marcelo C Mendonça, Ricardo C Calhelha, Isabel C F R Ferreira, Elton Franceschi, Francine F Padilha, Maria Beatriz P P Oliveira, Cláudio Dariva
Azadirachta indica A. Juss (neem) extracts have been used in pharmaceutical applications as antitumor agents, due to their terpenes and phenolic compounds. To obtain extracts from neem leaves with potential antiproliferative effect, a sequential process of pressurized liquid extraction was carried out in a fixed bed extractor at 25 °C and 100 bar, using hexane (SH), ethyl acetate (SEA), and ethanol (SE) as solvents. Extractions using only ethanol (EE) was also conducted to compare the characteristics of the fractionated extracts...
July 30, 2018: Pharmaceuticals
Reinhard Stidl, Michael Denne, Jimena Goldstine, Bill Kadish, Katherine I Korakas, Peter L Turecek
Polyethylene glycol (PEG) is an inert, water soluble polymer, used for decades in pharmaceuticals. Although PEG is considered safe, concerns persist about the potential adverse effects of long-term exposure to PEG-containing therapies, specifically in children, following the introduction of PEGylated recombinant factor products used for the treatment of hemophilia. Given the absence of long-term surveillance data, and to evaluate the potential risk, we estimated PEG exposure in the pediatric population receiving PEGylated therapies with pediatric indications administered intravenously or intramuscularly...
July 26, 2018: Pharmaceuticals
Zaril H Zakaria, Alan Y Y Fong, Raj K S Badhan
Malaysia is a multi-ethnic society whereby the impact of pharmacogenetic differences between ethnic groups may contribute significantly to variability in clinical therapy. One of the leading causes of mortality in Malaysia is cardiovascular disease (CVD), which accounts for up to 26% of all hospital deaths annually. Clopidogrel is used as an adjunct treatment in the secondary prevention of cardiovascular events. CYP2C19 plays an integral part in the metabolism of clopidogrel to the active metabolite clopi-H4...
July 26, 2018: Pharmaceuticals
Nataliia Melnichuk, Vladimir Kashuba, Svitlana Rybalko, Zenoviy Tkachuk
Rapid replication of the influenza A virus and lung tissue damage caused by exaggerated pro-inflammatory host immune responses lead to numerous deaths. Therefore, novel therapeutic agents that have anti-influenza activities and attenuate excessive pro-inflammatory responses that are induced by an influenza virus infection are needed. Oligoribonucleotides-d-mannitol (ORNs-d-M) complexes possess both antiviral and anti-inflammatory activities. The current research was aimed at studying the ORNs-d-M effects on expression of innate immune genes in mice lungs during an influenza virus infection...
July 22, 2018: Pharmaceuticals
Mayara Amoras Teles Fujishima, Nayara Dos Santos Raulino da Silva, Ryan da Silva Ramos, Elenilze Figueiredo Batista Ferreira, Kelton Luís Belém Dos Santos, Carlos Henrique Tomich de Paula da Silva, Jocivania Oliveira da Silva, Joaquín Maria Campos Rosa, Cleydson Breno Rodrigues Dos Santos
Reactive oxygen species (ROS) are continuously generated in the normal biological systems, primarily by enzymes as xanthine oxidase (XO). The inappropriate scavenging or inhibition of ROS has been considered to be linked with aging, inflammatory disorders, and chronic diseases. Therefore, many plants and their products have been investigated as natural antioxidants for their potential use in preventive medicine. The leaves and bark extracts of Curatella americana Linn. were described in scientific research as anti-inflammatory, vasodilator, anti-ulcerogenic, and hypolipidemic effects...
July 20, 2018: Pharmaceuticals
Sorah Yoon, John J Rossi
Imaging is not only seeing, but also believing. For targeted imaging modalities, nucleic acid aptamers have features such as superior recognition of structural epitopes and quick uptake in target cells. This explains the emergence of an evolved new class of aptamers into a wide spectrum of imaging applications over the last decade. Genetically encoded biosensors tagged with fluorescent RNA aptamers have been developed as intracellular imaging tools to understand cellular signaling and physiology in live cells...
July 19, 2018: Pharmaceuticals
Alessandra Boschi, Micòl Pasquali, Claudio Trapella, Alessandro Massi, Petra Martini, Adriano Duatti, Remo Guerrini, Vinicio Zanirato, Anna Fantinati, Erika Marzola, Melchiore Giganti, Licia Uccelli
BACKGROUND: New approaches based on the receptor-targeted molecular interaction have been recently developed with the aim to investigate specific probes for sentinel lymph nodes. In particular, the mannose receptors expressed by lymph node macrophages became an attractive target and different multifunctional mannose derivate ligands for the labeling with 99m Tc have been developed. In this study, we report the synthesis of a specific class of dextran-based, macromolecular, multifunctional ligands specially designed for labeling with the highly stable [99m Tc≡N]2+ core...
July 16, 2018: Pharmaceuticals
Ismail Hdoufane, Imane Bjij, Mahmoud Soliman, Alia Tadjer, Didier Villemin, Jane Bogdanov, Driss Cherqaoui
Quantitative Structure Activity Relationships (QSAR or SAR) have helped scientists to establish mathematical relationships between molecular structures and their biological activities. In the present article, SAR studies have been carried out on 89 tetrahydroimidazo[4,5,1-jk][1,4]benzodiazepine (TIBO) derivatives using different classifiers, such as support vector machines, artificial neural networks, random forests, and decision trees. The goal is to propose classification models that will be able to classify TIBO compounds into two groups: high and low inhibitors of HIV-1 reverse transcriptase...
July 13, 2018: Pharmaceuticals
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