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New Drugs

Godwin U Ebiloma, Teresa Díaz Ayuga, Emmanuel O Balogun, Lucía Abad Gil, Anne Donachie, Marcel Kaiser, Tomás Herraiz, Daniel K Inaoka, Tomoo Shiba, Shigeharu Harada, Kiyoshi Kita, Harry P de Koning, Christophe Dardonville
African trypanosomiasis is a neglected parasitic disease that is still of great public health relevance, and a severe impediment to agriculture in endemic areas. The pathogens possess certain unique metabolic features that can be exploited for the development of new drugs. Notably, they rely on an essential, mitochondrially-localized enzyme, Trypanosome Alternative Oxidase (TAO) for their energy metabolism, which is absent in the mammalian hosts and therefore an attractive target for the design of safe drugs...
February 26, 2018: European Journal of Medicinal Chemistry
Yi-Lei Fan, Xiao-Hong Jin, Zhong-Ping Huang, Hai-Feng Yu, Zhi-Gang Zeng, Tao Gao, Lian-Shun Feng
Tuberculosis still remains one of the most common, communicable, and leading deadliest diseases known to mankind throughout the world. Drug-resistance in Mycobacterium tuberculosis which threatens to worsen the global tuberculosis epidemic has caused great concern in recent years. To overcome the resistance, the development of new drugs with novel mechanisms of actions is of great importance. Imidazole-containing derivatives endow with various biological properties, and some of them demonstrated excellent anti-tubercular activity...
March 7, 2018: European Journal of Medicinal Chemistry
Vesa M Olkkonen, Juha Sinisalo, Matti Jauhiainen
Remarkably good results have been achieved in the treatment of atherosclerotic cardiovascular diseases (CVD) by using statin, ezetimibe, antihypertensive, antithrombotic, and PCSK9 inhibitor therapies and their proper combinations. However, despite this success, the remaining CVD risk is still high. To target this residual risk and to treat patients who are statin-intolerant or have an exceptionally high CVD risk for instance due to familial hypercholesterolemia (FH), new therapies are intensively sought. One pathway of drug development is targeting the circulating triglyceride-rich lipoproteins (TRL) and their lipolytic remnants, which, according to the current view, confer a major CVD risk...
March 8, 2018: Atherosclerosis
Yuyan Gao, Li Li, David C Schwebel, Peishan Ning, Peixia Cheng, Guoqing Hu
Social medical insurance schemes are crucial for realizing universal health coverage and health equity. The aim of this study was to investigate whether and how reimbursement for injury-induced medical expenses is addressed in Chinese legislative documents relevant to social medical insurance. We retrieved legislative documents from the China National Knowledge Infrastructure and the Lawyee databases. Four types of social medical insurance schemes were included: urban employee basic medical insurance, urban resident basic medical insurance, new rural cooperative medical system, and urban and rural resident medical insurance...
2018: PloS One
Mariana Matias, Samuel Silvestre, Amílcar Falcão, Gilberto Alves
Purpose - During the discovery and development of new drugs, compounds with low aqueous solubility pose special challenges in their pharmacological evaluation and, therefore, the selection of appropriate vehicles to administer the compounds of interest is determinant for the quality of the results generated during the in vivo non-clinical studies. This work aimed to evaluate the motor deficit (as a surrogate of neurotoxicity) of several administration/delivery vehicles through the rotarod performance test. Methods - Trained male CD-1 mice were intraperitoneally administered with the following vehicles: dimethyl sulfoxide (DMSO), aqueous sodium chloride (NaCl) 0...
2018: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
Mohammed Saji Salahudeen, Prasad S Nishtala
OBJECTIVE: To summarize studies that used the international Resident Assessment home care instrument (interRAI HC) to examine study outcomes for older people. METHODS: A comprehensive systematic search was performed to identify relevant studies, using five databases from 1990 until October 2016. The Cochrane Risk-Bias assessment tool and Newcastle-Ottawa Scale was used to assess the quality of RCTs and non-RCTs, respectively. RESULTS: Based on the full-text analysis, 40 studies met the inclusion criteria out of 506 total records...
March 2, 2018: Clinical Gerontologist
Norelle Sherry, Benjamin Howden
Multidrug-resistant (MDR) and extensively-drug-resistant (XDR) Gram-negative bacteria have emerged as a major threat to human health globally. This has resulted in the "re-discovery" of some older antimicrobials and development of new agents, however resistance has also rapidly emerged to these agents. Areas Covered: Here we describe recent developments in resistance to three of the most important last-line antimicrobials for treatment of MDR and XDR Gram negatives: fosfomycin, colistin and ceftazidime-avibactam...
March 15, 2018: Expert Review of Anti-infective Therapy
Rajendra H Patil, Firoz A Kalam Khan, Kaivalya Jadhav, Manoj Damale, Siddique Akber Ansari, Hamad M Alkahtani, Azmat Ali Khan, Shantanu D Shinde, Rajesh Patil, Jaiprakash N Sangshetti
We report the synthesis of some new piperazine-sulphonamide linked Schiff bases as fungal biofilm inhibitors with antibacterial and antifungal potential. The biofilm inhibition result of Candida albicans proposed that the compounds 6b (IC50  = 32.1 μM) and 6j (IC50  = 31.4 μM) showed higher inhibitory activity than the standard fluconazole (IC50  = 40 μM). Compound 6d (MIC = 26.1 μg/mL) with a chloro group at the para position was found to be the most active antibacterial agent of the series against Bacillus subtilis when compared with the standard ciprofloxacin (MIC = 50 μg/mL)...
March 15, 2018: Archiv der Pharmazie
A V Petrayevsky, K S Trishkin
Pterygium is one of the modern problems of ophthalmology. The exact etiology and pathogenesis of this disease has not been reliably established and, as a result, there is no universal method for its recurrence-free treatment. The literature data on various methods of pterygium surgical treatment such as 'bare sclera', conjunctival autograft, limbal stem cells transplantation techniques, amniotic membrane plasty and other methods was analyzed. The advantages and disadvantages of those surgery methods were identified...
2018: Vestnik Oftalmologii
Stephan R Bohl, Lars Bullinger, Frank G Rücker
The majority of patients with acute myeloid leukemia (AML) are older and exhibit a poor prognosis even after intensive therapy. Inducing differentiation and apoptosis of leukemic blasts by DNA-hypomethylating agents, like e.g. azacytidine (AZA) and decitabine (DAC), represent well-tolerated alternative treatment approaches. Both agents show convincing response as single agents in AML. However, there is a lack of knowledge regarding molecular mechanisms and predictive biomarkers for these agents. Areas covered: This review will (i) provide an overview of the current knowledge of molecular mechanisms underlying the action of these drugs, (ii) report promising predictive biomarkers, (iii) elude on new combined treatment options, and (iv) discuss novel approaches to improve outcomes...
March 15, 2018: Expert Review of Hematology
Geraldine Dowling, Pierce V Kavanagh, Hans-Georg Eckhardt, Brendan Twamley, Gary Hessman, Gavin McLaughlin, John O' Brien, Simon D Brandt
Nitrazolam and clonazolam are two designer benzodiazepines that are available from internet retailers and there is growing evidence suggesting that such compounds have the potential to cause severe adverse events. Information about tolerability in humans is scarce but typically, low doses can be difficult to administer for users when handling bulk material and variability of the active ingredient in tablet formulations can also be of a concern. Customs, toxicology and forensic laboratories are increasingly encountering designer benzodiazepines, both in tablet and powdered forms, and the unavailability of reference standards can impact on the ability to identify these compounds...
March 15, 2018: Drug Testing and Analysis
Nongluk Sriwilaijaroen, Shin-Ichi Nakakita, Sachiko Kondo, Hirokazu Yagi, Koichi Kato, Takeomi Murata, Hiroaki Hiramatsu, Toshio Kawahara, Yohei Watanabe, Yasushi Kanai, Takao Ono, Jun Hirabayashi, Kazuhiko Matsumoto, Yasuo Suzuki
The rapidly evolvable influenza A virus has caused pandemics linked to millions of deaths in the past century. Influenza A viruses are categorized by H (hemagglutinin; HA) and N (neuraminidase; NA) proteins expressed on the viral envelope surface. Analyses of past pandemics suggest that the HA gene segment comes from a nonhuman virus, which is then introduced into an immunologically naïve human population with potentially devastating consequences. As a prerequisite for infection, the nonhuman HA molecules of H1-H16 viruses must be able to bind to specific sialyl receptors on the host cell surface along the human respiratory tract...
March 15, 2018: FEBS Journal
Liwen Feng, Don Antoine Lanfranchi, Leandro Cotos, Elena Cesar-Rodo, Katharina Ehrhardt, Alice-Anne Goetz, Herbert Zimmermann, François Fenaille, Stephanie A Blandin, Elisabeth Davioud-Charvet
Malaria is a tropical parasitic disease threatening populations in tropical and sub-tropical areas. Resistance to antimalarial drugs has spread all over the world in the past 50 years, thus new drugs are urgently needed. Plasmodione (benzylmenadione series) has been identified as a potent antimalarial early lead drug, acting through a redox bioactivation on asexual and young sexual blood stages. To investigate its metabolism, a series of plasmodione-based tools, including a fully13 C-labelled lead drug and putative metabolites, have been designed and synthesized for drug metabolism investigation...
March 15, 2018: Organic & Biomolecular Chemistry
Wei Sun, Ju-Dong Luo, Hua Jiang, Dayue Darrel Duan
Tumor cells produce and secrete more nucleic acids, proteins and lipids than normal cells. These molecules are transported in the blood or around the cells in membrane-encapsulated exosomes. Tumor-derived or tumor-associated exosomes (usually 30-100 nm in diameter) contain abundant biological contents resembling those of the parent cells along with signaling messengers for intercellular communication involved in the pathogenesis, development, progression, and metastasis of cancer. As these exosomes can be detected and isolated from various body fluids, they have become attractive new biomarkers for the diagnosis and prognosis of cancer...
March 15, 2018: Acta Pharmacologica Sinica
Paola Cipriani, Vasiliky Liakouli, Francesco Carubbi, Onorina Berardicurti, Paola Di Benedetto, Francesco Ciccia, Giuliana Guggino, Saverio Alvaro, Giovanni Triolo, Roberto Giacomellia, Piero Ruscitti
BACKGROUND: Although in the past, prevention of the joint destruction and disability were strongly emphasised in rheumatoid arthritis (RA), at present, a growing body of evidence is focused at identifying the best management of associated comorbidities, such as type 2 diabetes (T2D). Recently, the hypothesis that blocking pro-inflammatory activity may be helpful in the treatment of some comorbidities has been proposed in RA patients. OBJECTIVE: We reviewed the role of IL-1β during RA and T2D, the efficacy of IL-1 blocking agents in controlling both diseases and, possible, decreasing the concomitant enhanced atherosclerotic process...
March 13, 2018: Reviews on Recent Clinical Trials
Akhil Kumar, Ashish Tiwari, Ashok Sharma
Alzheimer disease (AD) is now considered as a multifactorial neurodegenerative disorder and rapidly increasing to an alarming situation and causing higher death rate. One target one ligand hypothesis is not able to provide complete solution of AD due to multifactorial nature of disease and one target one drug seems to fail to provide better treatment against AD. Moreover, current available treatments are limited and most of the upcoming treatments under clinical trials are based on modulating single target...
March 15, 2018: Current Neuropharmacology
Sheikh Arslan Sehgal, Mirza A Hammad, Rana Adnan Tahir, Hafiza Nisha Akram, Faheem Ahmad
BACKGROUND: As the number of elderly persons increases, neurodegenerative diseases are becoming ubiquitous. There is currently a great need for knowledge concerning management of old-age neurodegenerative diseases; the most important of which are: Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis, and Huntington's disease. OBJECTIVE: To summarize the potential of computationally predicted molecules and targets against neurodegenerative diseases...
March 15, 2018: Current Neuropharmacology
Scott Pardo, Rimma M Shaginian, David A Simmons
BACKGROUND: Diabetes treatment is intended to maintain near-normal glycemic levels. Self-monitoring of blood glucose (SMBG) allows patients to track their BG levels compared with glycemic targets and is associated with improved health outcomes. Because of the importance of SMBG, it is essential that results are accurate to prevent errors in nutritional intake and drug dosing. This study presents a new methodology to evaluate the accuracy of BG monitoring systems (BGMSs). METHODS: Sensitivity analyses were performed using real and simulated BGMS data to compute probabilities that, for any BG value, the BGMS result would be within prescribed error bounds and confidence limits compared with laboratory reference values...
March 1, 2018: Journal of Diabetes Science and Technology
Daniel Geh, Caroline Gordon
Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease. There are three drugs licensed for the treatment of lupus: corticosteroids, hydroxychloroquine and belimumab. Immunosuppressants such as azathioprine, methotrexate and mycophenolate are also used. Despite these treatments there is still considerable morbidity. New treatments are needed for the management of active lupus. Epratuzumab a humanized IgG1 monoclonal antibody that targets CD22 resulting in selective B cell modulation that has been considered a potential treatment for SLE...
March 15, 2018: Expert Review of Clinical Immunology
Pamela Orjuela-Sanchez, Zaira Hellen Villa, Marta Moreno, Carlos Tong-Rios, Stephan Meister, Gregory M LaMonte, Brice Campo, Joseph M Vinetz, Elizabeth A Winzeler
To develop new drugs and vaccines for malaria elimination, it will be necessary to discover biological interventions, including small molecules that act against Plasmodium vivax exoerythrocytic forms. However, a robust in vitro culture system for P. vivax is still lacking. Thus, to study exoerythrocytic forms, researchers must have simultaneous access to fresh, temperature-controlled patient blood samples, as well as an anopheline mosquito colony. In addition, researchers must rely on native mosquito species to avoid introducing a potentially dangerous invasive species into a malaria-endemic region...
March 15, 2018: ACS Infectious Diseases
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