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Eva Rico, Laura Jeacock, Julie Kovářová, David Horn
The Cas9 endonuclease can be programmed by guide RNA to introduce sequence-specific breaks in genomic DNA. Thus, Cas9-based approaches present a range of novel options for genome manipulation and precision editing. African trypanosomes are parasites that cause lethal human and animal diseases. They also serve as models for studies on eukaryotic biology, including 'divergent' biology. Genome modification, exploiting the native homologous recombination machinery, has been important for studies on trypanosomes but often requires multiple rounds of transfection using selectable markers that integrate at low efficiency...
May 21, 2018: Scientific Reports
Qin Liu, Xiao-Ling Chen, Mu-Xin Chen, Han-Guo Xie, Qing Liu, Zhu-Yun Chen, Yao-Ying Lin, Hua Zheng, Jia-Xu Chen, Yi Zhang, Xiao-Nong Zhou
BACKGROUND: Human African trypanosomiasis (HAT) is one of the most complex parasitic diseases known to humankind. It usually occurs in endemic areas in Africa, but is occasionally detected in returning travelers and migrants in non-endemic countries. CASE PRESENTATION: In August 2017, a case of HAT was diagnosed in China in a traveler returning from the Masai Mara area in Kenya and the Serengeti area in Tanzania. The traveler visited Africa from 23 July to 5 August, 2017...
May 21, 2018: Infectious Diseases of Poverty
Felise G Adams, Uwe H Stroeher, Karl A Hassan, Shashikanth Marri, Melissa H Brown
In recent years, effective treatment of infections caused by Acinetobacter baumannii has become challenging due to the ability of the bacterium to acquire or up-regulate antimicrobial resistance determinants. Two component signal transduction systems are known to regulate expression of virulence factors including multidrug efflux pumps. Here, we investigated the role of the AdeRS two component signal transduction system in regulating the AdeAB efflux system, determined whether AdeA and/or AdeB can individually confer antimicrobial resistance, and explored the interplay between pentamidine resistance and growth conditions in A...
2018: PloS One
Ioan O Neaga, Stephanie Hambye, Ede Bodoki, Claudio Palmieri, Eugénie Ansseau, Alexandra Belayew, Radu Oprean, Bertrand Blankert
Myotonic dystrophy type 1 (DM1) is an autosomal dominantly inherited degenerative disease with a slow progression. At the present, there is no commercially available treatment, but sustained effort is currently undertaken for the development of a promising lead compound. In the present paper we report the development of a fast, versatile, and cost-effective affinity capillary electrophoresis (ACE) method for the screening and identification of potential drug candidates targeting pathological ARN probes relevant for DM1...
May 8, 2018: Analytical and Bioanalytical Chemistry
A Oryan, E Bemani, S Bahrami
Leishmaniasis is a group of human and animal diseases causing 20,000 to 40,000 annual deaths and its etiological agents belong to the Leishmania genus. The most current treatment against leishmaniasis is chemotherapy. Pentavalent antimonials such as glucantime and pentostam have been administrated as the first-line drugs in treatment of various forms of leishmaniasis. The second-line drugs such as amphotericin B, liposomal amphotericin B, miltefosine, pentamidine, azole drugs and paromomycin are used in resistant cases to pentavalent antimonials...
April 21, 2018: Acta Tropica
C A Wijsman, J L J Hanssen, H Scheper, L G Visser, L van Lieshout
We present a case of East-African trypanosomiasis (EAT) in a 56-year-old Dutch woman returning from holiday in Tanzania and Kenya. The diagnosis was delayed due to the lack of suspicion and secondly because of postponed analysis of blood microscopy after negative rapid malaria antigen testing. Second stage trypanosomiasis was ruled out with liquor analysis. She was treated first with pentamidine and shortly thereafter with suramin, after which she recovered. We emphasize the use of thin/thick smear diagnostics in travellers returning from endemic countries...
January 1, 2018: Journal of Travel Medicine
Federica Rinaldi, Patrizia N Hanieh, Lik King Nicholas Chan, Livia Angeloni, Daniele Passeri, Marco Rossi, Julie Tzu-Wen Wang, Anna Imbriano, Maria Carafa, Carlotta Marianecci
The aim of this in vitro study is to prepare and characterize drug free and pentamidine loaded chitosan glutamate coated niosomes for intranasal drug delivery to reach the brain through intranasal delivery. Mucoadhesive properties and stability testing in various environments were evaluated to examine the potential of these formulations to be effective drug delivery vehicles for intranasal delivery to the brain. Samples were prepared using thin film hydration method. Changes in size and ζ-potential of coated and uncoated niosomes with and without loading of pentamidine in various conditions were assessed by dynamic light scattering (DLS), while size and morphology were also studied by atomic force microscopy (AFM)...
March 22, 2018: Pharmaceutics
Alfonso Molina, Drew J Winston, Darren Pan, Gary J Schiller
Nocardial infections have been rare after allogeneic hematopoietic stem cell transplantation (HSCT). We report 10 recent cases of late-onset nocardiosis (median time of onset of 508 days after transplantation) primarily in patients on high doses of corticosteroids for graft-versus-host disease (GVHD). All 10 patients had pulmonary infection caused by Nocardia species susceptible to trimethoprim-sulfamethoxazole (TMP-SMX). At time of diagnosis, 8 of 10 patients were not receiving TMP-SMX for prophylaxis of Pneumocystis jiroveci pneumonia (PJP) (7 on atovaquone, 1 on intravenous pentamidine)...
March 16, 2018: Biology of Blood and Marrow Transplantation
Penta Ashok, Subhash Chander, Terry K Smith, Murugesan Sankaranarayanan
Molecular hybridization is a ligand based drug design approach is well known recent medicinal chemistry to design anti-parasitic agents. In the present study, we have designed a series of (1-phenyl-9H-pyrido [3,4-b]indol-3-yl) (4-phenylpiperazin-1-yl)methanone derivatives using molecular hybridization approach. Designed analogues were evaluated for cytotoxicity and inhibition activity against Leishmania infantum and Leishmania donovani. Among these reported analogues 7b, 7d, 7e, 7f and 7m displayed potent inhibition of both L...
April 25, 2018: European Journal of Medicinal Chemistry
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...
April 25, 2018: European Journal of Medicinal Chemistry
Jacques-Robert Christen, Eliane Bourreau, Magalie Demar, Edward Lightburn, Pierre Couppié, Marine Ginouvès, Ghislaine Prévot, Jean-Pierre Gangneux, Hélène Savini, Frank de Laval, Vincent Pommier de Santi, Sébastien Briolant
BACKGROUND: New world cutaneous leishmaniasis (NWCL) can be found in French Guiana as well as in several other parts of Central and South America. Leishmania guyanensis accounts for nearly 90% of cases in French Guiana and is treated with pentamidine isethionate, given by either intramuscular or intravenous injection. The military population is particularly exposed due to repeated missions in the rainforest. The purpose of the present study was to identify the factors associated with pentamidine isethionate treatment failure in a series of service members with L...
March 1, 2018: Travel Medicine and Infectious Disease
Valeska Albuquerque Francesconi, Fabio Francesconi, Rajendranath Ramasawmy, Gustavo Adolfo Sierra Romero, Maria das Graças Costa Alecrim
BACKGROUND: The treatment of Leishmaniasis caused by Leishmania (Viannia) guyanensis is based on a weak strength of evidence from very few clinical trials and some case series reports. Current treatment guidelines recommend pentamidine isethionate or meglumine antimoniate (Glucantime) as the first-line choices. Both are parenteral drugs with a low therapeutic indexes leading to a high risk of undesired effects. Imidazole derivatives interfere with the production of leishmanial ergosterol, an essential component of their membrane structure...
February 2018: PLoS Neglected Tropical Diseases
Róbson Ricardo Teixeira, Poliana Aparecida Rodrigues Gazolla, Adalberto Manoel da Silva, Maria Paula Gonçalves Borsodi, Bartira Rossi Bergmann, Rafaela Salgado Ferreira, Boniek Gontijo Vaz, Géssica Adriana Vasconcelos, Wallace Pacienza Lima
In this paper, it is described the synthesis and the evaluation of the leishmanicidal activity of twenty-six eugenol derivatives bearing 1,2,3-triazole functionalities. The evaluation of the compounds on promastigotes of Leishmania amazonensis (WHOM/BR/75/Josefa) showed that eugenol derivatives present leishmanicidal activities with varying degrees of effectiveness. The most active compound, namely 4-(3-(4-allyl-2-methoxyphenoxy)propyl)-1-(4-methylbenzyl)-1H-1,2,3-triazole (7k) (IC50  = 7.4 ± 0.8 μmol L-1 ), also targeted Leishmania parasites inside peritoneal macrophages (IC50  = 1...
February 25, 2018: European Journal of Medicinal Chemistry
Letícia de Almeida, Andressa Terumi Fujimura, Mayara Lucia Del Cistia, Bruno Fonseca-Santos, Kely Braga Imamura, Paul A M Michels, Marlus Chorilli, Márcia A S Graminha
The World Health Organization (WHO) estimates that more than one billion people suffer from neglected tropical diseases. Leishmaniasis is a widespread disease, affecting 12 million people around the world with about 1–2 million estimated new cases occurring every year. Although pentavalent antimonial drugs are the most frequently prescribed treatments for leishmaniasis, they produce severe side effects, including cardiotoxicity and hepatotoxicity. Other compounds, such as amphotericin B, pentamidine and miltefosine, are second choice drugs, but they also produce side effects that can endanger the patient's life...
February 2017: Journal of Biomedical Nanotechnology
Nida Ghouri, Khalid Mohammed Khan, Arshia, M Iqbal Choudhary, Shahnaz Perveen
BACKGROUND: Leishmaniasis is a protozoan parasitic vector-borne disease which is endemic in 88 tropical countries. Infected sand fly is the main cause of this disease while, there are several vectors, parasites, and reservoirs involved in the transmission of this disease. Leishmania donovani, L. infantum, and L. chagasi are. common disease causing species, spread through sandflies. It is considered to be a focal disease having scattered foci. Leishmaniasis is a disease with a broad clinical spectrum...
January 14, 2018: Medicinal Chemistry
Silvia Spoto, Sebastiano Costantino, Emanuele Valeriani, Marta Fogolari, Eleonora Cella, Giordano Dicuonzo, Massimo Ciccozzi, Silvia Angeletti
Adult-onset Still's disease (AOSD) due to visceral leishmaniasis (VL) has not been previously reported. This case report analyzes a single episode of AOSD probably due to a visceral leishmaniasis successfully treated with pentamidine isethionate and prednisone.
December 2017: Clinical Case Reports
Angela Scala, Anna Piperno, Nicola Micale, Placido G Mineo, Antonio Abbadessa, Roberta Risoluti, Germano Castelli, Federica Bruno, Fabrizio Vitale, Antonio Cascio, Giovanni Grassi
Pentamidine (Pent), an antiparasitic drug used for the treatment of visceral leishmaniasis, has been modified with terminal azide groups and conjugated to two different polymer backbones (PLGA-PEG [PP] copolymer and hyaluronic acid [HA]) armed with alkyne end-groups. The conjugation has been performed by Copper Catalyzed Azido Alkyne Cycloaddition (CuAAC) using CuSO4 /sodium ascorbate as metal source. The novel PP-Pent and HA-Pent bioconjugates are proposed, respectively, as non-targeted and targeted drug delivery systems against Leishmania infections...
December 8, 2017: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
Yoshiyuki Ohara, Takanori Asakura, Soichiro Ueda, Yoshitake Yamada, Makoto Ishii, Tomoko Betsuyaku
No abstract text is available yet for this article.
December 1, 2017: QJM: Monthly Journal of the Association of Physicians
Jung-Ren Chen, Yu-Heng Lai, Jhih-Jie Tsai, Chung-Der Hsiao
Currently, drug screening relies on cell-based experiments or on animal models to confirm biological effects. The mammalian system is considered too time-consuming, expensive and complex to perform high-throughput drug screening. There is a gap between in vitro cell-based models and the in vivo mammalian models. The zebrafish is an ideal model that could link preclinical toxicity screening with the drug development pipeline. Taking advantage of a highly conservative genomic, rapid development, large number of offspring, low cost and easy manipulation, zebrafish has been considered an excellent animal model for disease-based drug screening...
November 27, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Kah Tee Lim, Azimah Amanah, Nelson Jeng-Yeou Chear, Zuriati Zahari, Zafarina Zainuddin, Mohd Ilham Adenan
In our ongoing work searching for new trypanocidal lead compounds from Malaysian plants, two known piperidine alkaloids (+)-spectaline (1) and iso-6-spectaline (2) were isolated from the leaves of Senna spectabilis (sin. Cassia spectabilis). Analysis of the1 H and13 C NMR spectra showed that 1 and 2 presented analytical and spectroscopic data in full agreement with those published in the literature. All compounds were screened in vitro against Trypanosoma brucei rhodesiense in comparison to the standard drug pentamidine...
January 2018: Experimental Parasitology
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