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Maureen Mackintosh, Julius Mugwagwa, Geoffrey Banda, Paula Tibandebage, Jires Tunguhole, Samuel Wangwe, Mercy Karimi Njeru
The benefits of local production of pharmaceuticals in Africa for local access to medicines and to effective treatment remain contested. There is scepticism among health systems experts internationally that production of pharmaceuticals in sub-Saharan Africa (SSA) can provide competitive prices, quality and reliability of supply. Meanwhile low-income African populations continue to suffer poor access to a broad range of medicines, despite major international funding efforts. A current wave of pharmaceutical industry investment in SSA is associated with active African government promotion of pharmaceuticals as a key sector in industrialization strategies...
March 19, 2018: Health Policy and Planning
Mark Sherman, Lydia Contreras
Recent advances in computational and experimental methods have led to novel avenues for therapeutic development. Utilization of nucleic acids as therapeutic agents and/or targets has been recently gaining attention due to their potential as high-affinity, selective molecular building blocks for various therapies. Notably, development of computational algorithms for predicting accessible RNA binding sites, identifying therapeutic target sequences, modeling delivery into tissues, and designing binding aptamers have enhanced therapeutic potential for this new drug category...
March 18, 2018: Current Opinion in Biotechnology
Noura S Abul-Husn, Xiping Cheng, Alexander H Li, Yurong Xin, Claudia Schurmann, Panayiotis Stevis, Yashu Liu, Julia Kozlitina, Stefan Stender, G Craig Wood, Ann N Stepanchick, Matthew D Still, Shane McCarthy, Colm O'Dushlaine, Jonathan S Packer, Suganthi Balasubramanian, Nehal Gosalia, David Esopi, Sun Y Kim, Semanti Mukherjee, Alexander E Lopez, Erin D Fuller, John Penn, Xin Chu, Jonathan Z Luo, Uyenlinh L Mirshahi, David J Carey, Christopher D Still, Michael D Feldman, Aeron Small, Scott M Damrauer, Daniel J Rader, Brian Zambrowicz, William Olson, Andrew J Murphy, Ingrid B Borecki, Alan R Shuldiner, Jeffrey G Reid, John D Overton, George D Yancopoulos, Helen H Hobbs, Jonathan C Cohen, Omri Gottesman, Tanya M Teslovich, Aris Baras, Tooraj Mirshahi, Jesper Gromada, Frederick E Dewey
BACKGROUND: Elucidation of the genetic factors underlying chronic liver disease may reveal new therapeutic targets. METHODS: We used exome sequence data and electronic health records from 46,544 participants in the DiscovEHR human genetics study to identify genetic variants associated with serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Variants that were replicated in three additional cohorts (12,527 persons) were evaluated for association with clinical diagnoses of chronic liver disease in DiscovEHR study participants and two independent cohorts (total of 37,173 persons) and with histopathological severity of liver disease in 2391 human liver samples...
March 22, 2018: New England Journal of Medicine
Robert J Motzer, Nizar M Tannir, David F McDermott, Osvaldo Arén Frontera, Bohuslav Melichar, Toni K Choueiri, Elizabeth R Plimack, Philippe Barthélémy, Camillo Porta, Saby George, Thomas Powles, Frede Donskov, Victoria Neiman, Christian K Kollmannsberger, Pamela Salman, Howard Gurney, Robert Hawkins, Alain Ravaud, Marc-Oliver Grimm, Sergio Bracarda, Carlos H Barrios, Yoshihiko Tomita, Daniel Castellano, Brian I Rini, Allen C Chen, Sabeen Mekan, M Brent McHenry, Megan Wind-Rotolo, Justin Doan, Padmanee Sharma, Hans J Hammers, Bernard Escudier
Background Nivolumab plus ipilimumab produced objective responses in patients with advanced renal-cell carcinoma in a pilot study. This phase 3 trial compared nivolumab plus ipilimumab with sunitinib for previously untreated clear-cell advanced renal-cell carcinoma. Methods We randomly assigned adults in a 1:1 ratio to receive either nivolumab (3 mg per kilogram of body weight) plus ipilimumab (1 mg per kilogram) intravenously every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram) every 2 weeks, or sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle)...
March 21, 2018: New England Journal of Medicine
Aurelia Vasile, Maria Ignat, Mirela Fernanda Zaltariov, Liviu Sacarescu, Iulian Stoleriu, Dan Draganescu, Mihai Dumitras, Lacramioara Ochiuz
The present study reports the first time use of MCM-41 mesoporous silica as highly efficient carrier for bexarotene - an antineoplastic agent specific for cutaneous T-cell lymphoma treatment. Bexarotene is highly toxic and poor-water soluble, having low bioavailability in the conventional pharmaceutical forms. Comparative uptake of bexarotene on amino-functionalized silica host at various functionalization degrees is discussed in details taking into account all structural features, of matrix as well as properties of the drug molecules...
March 2018: Acta Chimica Slovenica
Mohamed Ezzat Khalifa
Aminothiazole nuclei and their various derivatives have been long used as precursors for the synthesis of biologically active molecules. As a typical heterocyclic amine, 2-aminothiazole is a cornerstone for the synthesis of many compounds, including sulfur drugs, biocides, fungicides, various types of dyes for synthetic fibers and chemical reaction accelerators and as intermediates in the synthesis of antibiotics, where a large number of 2-aminothiazoles have been substituted with different groups for various pharmaceutical purposes, besides their activity as corrosion inhibitors for mild steel protection as well...
March 2018: Acta Chimica Slovenica
Panteleimon D Mavroudis, Helen E Hermes, Donato Teutonico, Thomas G Preuss, Sebastian Schneckener
The environmental fates of pharmaceuticals and the effects of crop protection products on non-target species are subjects that are undergoing intense review. Since measuring the concentrations and effects of xenobiotics on all affected species under all conceivable scenarios is not feasible, standard laboratory animals such as rabbits are tested, and the observed adverse effects are translated to focal species for environmental risk assessments. In that respect, mathematical modelling is becoming increasingly important for evaluating the consequences of pesticides in untested scenarios...
2018: PloS One
Kate S Collison, Angela Inglis, Sherin Shibin, Soad Saleh, Bernard Andres, Rosario Ubungen, Jennifer Thiam, Princess Mata, Futwan A Al-Mohanna
RATIONALE: Aspartame (L-aspartyl phenylalanine methyl ester) is a non-nutritive sweetener (NNS) approved for use in more than 6000 dietary products and pharmaceuticals consumed by the general public including adults and children, pregnant and nursing mothers. However a recent prospective study reported a doubling of the risk of being overweight amongst 1-year old children whose mothers consumed NNS-sweetened beverages daily during pregnancy. We have previously shown that chronic aspartame (ASP) exposure commencing in utero may detrimentally affect adulthood adiposity status, glucose metabolism and aspects of behavior and spatial cognition, and that this can be modulated by developmental N-methyl-D-aspartate receptor (NMDAR) blockade with the competitive antagonist CGP 39551 (CGP)...
2018: PloS One
Chrysovalantis Voutouri, Triantafyllos Stylianopoulos
Hyaluronan is abundant in the extracellular matrix of many desmoplastic tumors and determines in large part the tumor biochemical and mechanical microenvironment. Additionally, it has been identified as one of the major physiological barriers to the effective delivery of drugs to solid tumors and its targeting with the use of pharmaceutical agents has shown to decompress tumor blood vessels, and thus improve tumor perfusion and efficacy of cytotoxic drugs. In this study, we investigated the contribution of hyaluronan to the accumulation of mechanical forces in tumors...
2018: PloS One
Beatrice Xuan Ho, Nicole Min Qian Pek, Boon-Seng Soh
The rising interest in human induced pluripotent stem cell (hiPSC)-derived organoid culture has stemmed from the manipulation of various combinations of directed multi-lineage differentiation and morphogenetic processes that mimic organogenesis. Organoids are three-dimensional (3D) structures that are comprised of multiple cell types, self-organized to recapitulate embryonic and tissue development in vitro. This model has been shown to be superior to conventional two-dimensional (2D) cell culture methods in mirroring functionality, architecture, and geometric features of tissues seen in vivo...
March 21, 2018: International Journal of Molecular Sciences
Jacinta C Conrad, Ryan Poling-Skutvik
Bacteria overwhelmingly live in geometrically confined habitats that feature small pores or cavities, narrow channels, or nearby interfaces. Fluid flows through these confined habitats are ubiquitous in both natural and artificial environments colonized by bacteria. Moreover, these flows occur on timeand length scales comparable to those associated with motility of bacteria and with the formation and growth of biofilms, which are surface-associated communities that house the vast majority of bacteria and protect them from host and environmental stresses...
March 21, 2018: Annual Review of Chemical and Biomolecular Engineering
Jin Huang, Wan Tang, Shengquan Zhu, Meini Du
Butyric acid (C3 H7 COOH) is an important chemical that is widely used in foodstuffs along with in the chemical and pharmaceutical industries. The bioproduction of butyric acid via large-scale fermentation has the potential to be more economical and efficient than petrochemical synthesis. In this paper, the metabolic pathways involved in the production of butyric acid from Clostridium tyrobutyricum using hexose and pentose as substrates are investigated, and approaches to enhance butyric acid production via genetic modification are discussed...
March 21, 2018: Preparative Biochemistry & Biotechnology
Xin Fang, Chun-Jiang Wang
Spirocyclic pyrrolidines are structural motifs frequently found in a wide variety of natural products, pharmaceuticals and biologically significant compounds. In the past few years, catalytic asymmetric 1,3-dipolar cycloaddition reactions of azomethine ylides have shown to be one of the most straightforward methods for the stereoselective preparation of diverse biologically important spiropyrrolidine heterocycles in high yields with excellent enantioselectivities under mild reaction conditions. In this review, we will discuss the recent major developments in the catalytic enantioselective synthesis of chiral spiropyrrolidine derivatives since 2009...
March 21, 2018: Organic & Biomolecular Chemistry
Shaymaa Abdalwahed Abdulameer
Background: Inadequate inhaled aerosol device demonstration and technique by health care professionals can lead to poor disease control. The aims of this study were to develop and validate Knowledge of Aerosol Tool (KAT) among registered and unregistered pharmacists and to assess the pharmaceutical care practice among registered pharmacists. Methods: The KAT and pharmaceutical care practice questionnaires were developed and modified from previous reports, then an observational cross-sectional study with a convenience sample size of 340 was carried out among registered and unregistered pharmacists...
2018: International Journal of Chronic Obstructive Pulmonary Disease
Yue Zhang, Liying Zhang, Qi Zhang, Xitong Zhang, Tong Zhang, Bing Wang
Background: Brucea javanica oil (BJO), a traditional Chinese herbal medicine, has a variety of pharmacological activities and several BJO-related patent drugs have been widely used in China. Purpose: The objective of this study was to evaluate the gastric therapeutic effects of self-made BJO and its pharmaceutical potential to formulate novel BJO gastroretentive floating bead by comparing with commercial products. Methods: BJO was extracted from the seeds of B...
2018: Drug Design, Development and Therapy
Laurence Vico, Alan Hargens
Space sojourns are challenging for life. The ability of the human body to adapt to these extreme conditions has been noted since the beginning of human space travel. Skeletal alterations that occur during spaceflight are now better understood owing to tools such as dual-energy X-ray densitometry and high-resolution peripheral quantitative CT, and murine models help researchers to understand cellular and matrix changes that occur in bone and that are difficult to measure in humans. However, questions remain with regard to bone adaptation and osteocyte fate, as well as to interactions of the skeleton with fluid shifts towards the head and with the vascular system...
March 21, 2018: Nature Reviews. Rheumatology
Dimitar Yonchev, Dilyana Dimova, Dagmar Stumpfe, Martin Vogt, Jürgen Bajorath
Public repositories of compounds and activity data are of prime importance for pharmaceutical research in academic and industrial settings. Major databases have evolved over the years. Their growth is accompanied by an increasing tendency toward data sharing. This is a positive development but not without potential problems. Using ChEMBL and PubChem as examples, we show that crosstalk between databases also leads to substantial data redundancy that might not be obvious. Redundancy is an important issue because it biases data analysis and knowledge extraction and leads to inflated views of available compounds, assays and activity data...
March 17, 2018: Drug Discovery Today
Refilwe Given Kudumela, Peter Masoko
There is very little scientific information on indigenous plants used for medicinal purposes. Therefore, the aim of the study was to evaluate the antibacterial and antioxidant activities of the leaves of Commelina africana, Elephantorrhiza elephantina, Dombeya rotundifolia, and the whole plant excluding the roots of Schkuhria pinnata indigenous medicinal plants from the Limpopo Province, which may be used for the treatment in humans infected with bacterial pathogens. The screening of different phytoconstituents using standard methods revealed the presence of terpenoids, flavonoids, tannins, and saponins...
January 2018: J Evid Based Integr Med
Francielle Tatiana Mathias, Douglas Henrique Fockink, Geonildo Rodrigo Disner, Viviane Prodocimo, João Luiz Coelho Ribas, Luiz Pereira Ramos, Marta Margarete Cestari, Helena Cristina Silva de Assis
Ibuprofen is a pharmaceutical drug widely used by the global population and it has been found in aquatic ecosystems in several countries. This study evaluated the effects of ibuprofen in environmental concentrations (0, 0.1, 1 and 10 μg/L) on the freshwaterspecies Rhamdia quelen exposed for 14 days. In the posterior kidney, ibuprofen increased glutathione-S-transferase activity in all groups exposed. Furthermore, increased glutathione peroxidase activity and the levels of reduced glutathione in the group exposed to 10 μg/L...
March 11, 2018: Environmental Toxicology and Pharmacology
Hidayat Hussain, Ivan R Green, Umair Shamraiz, Muhammad Saleem, Amin Badshah, Ghulam Abbas, Najeeb Ur Rehman, Muhammad Irshad
Glycyrrhetinic acids (GAs) viz., 18β-glycyrrhetinic acid and 18α-glycyrrhetinic acid, are oleanane-type triterpenes having a carboxylic acid group at C-30, and are extracted from the Chines herbal medicine licorice (Glycyrrhiza uralensis). Although the pharmacological properties of GAs have long been known, attention to them has greatly increased in recent times due to their cytotoxic activity. Areas Covered: This review represents the patents granted about natural and synthetic glycyrrhetinic acid analogs from January 2010 to December 2017, the advances made by research groups in conjunction with pharmaceutical companies in the discovery of new natural or synthetic glycyrrhetinic acid analogs...
March 20, 2018: Expert Opinion on Therapeutic Patents
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