Article
Biochemistry & Molecular Biology
Caue Benito Scarim, Francisco Olmo, Elizabeth Igne Ferreira, Chung Man Chin, John M. Kelly, Amanda Fortes Francisco
Summary: The research indicates that NFOH has stronger anti-Trypanosoma cruzi activity, works through a inhibitory mechanism, and is more effective in treating chronic infections compared to the acute stage, sharing similar characteristics with BZN.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Infectious Diseases
Amanda Fortes Francisco, Ursula Saade, Shiromani Jayawardhana, Hans Pottel, Ivan Scandale, Eric Chatelain, Peter Liehl, John M. Kelly, Maan Zrein
Summary: This study evaluated serological procedures for the diagnosis of T. cruzi infections and confirmation of parasitological cure using an experimental mouse model. The researchers identified a set of antigens that provide a rapid and accurate read-out of both acute and chronic T. cruzi infection. They also discovered specific antibody responses that can be correlated with parasite reduction or persistent infection. These findings could be used to develop diagnostic techniques and biomarkers for monitoring the efficacy of anti-T. cruzi drug treatment in a clinical setting.
PLOS NEGLECTED TROPICAL DISEASES
(2022)
Article
Infectious Diseases
Laura Jurado Medina, Emeric Chassaing, Griselda Ballering, Nicolas Gonzalez, Lola Marque, Peter Liehl, Hans Pottel, Jasper de Boer, Eric Chatelain, Maan Zrein, Jaime Altcheh
Summary: The study evaluated the MultiCruzi test as a predictive tool for parasitological cure in children with Chagas disease and found that it can predict seroreversion earlier than standard methods. In patients treated within the first year of age, MultiCruzi showed higher accuracy in predicting early seroreversion compared to traditional tests.
LANCET INFECTIOUS DISEASES
(2021)
Article
Biochemistry & Molecular Biology
Leonardo S. Lara, Guilherme C. Lechuga, Caroline dos S. Moreira, Thais B. Santos, Vitor F. Ferreira, David R. da Rocha, Mirian C. S. Pereira
Summary: Chagas disease remains a serious public health problem in Latin America, with current clinical treatments considered inadequate, emphasizing the need for discovering new effective and safe drugs. Research analyzed a series of naphthoquinone derivatives for biological activity and structure-activity relationship, identifying 1g as a promising compound against Trypanosoma cruzi. However, current compounds were unable to reduce parasite load or prevent mouse mortality in infection.
Article
Immunology
Julian Ernesto Nicolas Gulin, Margarita Maria Catalina Bisio, Daniela Rocco, Jaime Altcheh, Maria Elisa Solana, Facundo Garcia-Bournissen
Summary: This study evaluates the efficacy of Miltefosine (MLT) as a monodrug and combined with benznidazole (BZ) for treating Trypanosoma cruzi infection. MLT showed promising results in inhibiting the parasite in both in vitro and in vivo models, with improved efficacy when combined with BZ. This study provides support for the potential use of MLT in Chagas disease treatment and the exploration of combination therapies.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Review
Pharmacology & Pharmacy
Martin C. Taylor, Alexander Ward, Francisco Olmo, Amanda F. Francisco, Shiromani Jayawardhana, Fernanda C. Costa, Michael D. Lewis, John M. Kelly
Summary: Chagas disease is caused by infection with the trypanosomatid parasite Trypanosoma cruzi. Challenges in developing new drugs have been posed by the long term and complex nature of the condition and limited understanding of parasite biology. The development of noninvasive, highly sensitive bioluminescence imaging procedures based on red-shifted luciferase-expressing parasites has greatly improved infection monitoring and driven drug development.
CURRENT PHARMACEUTICAL DESIGN
(2021)
Article
Microbiology
Nieves Martinez-Peinado, Nuria Cortes-Serra, Julian Sherman, Ana Rodriguez, Juan M. Bustamante, Joaquim Gascon, Maria-Jesus Pinazo, Julio Alonso-Padilla
Summary: Chagas disease, caused by the parasite Trypanosoma cruzi, has its greatest burden in Latin America. Existing treatments present toxicity and variable efficacy, highlighting the urgent need for new therapeutic strategies. Drug repositioning offers a fast and low-cost approach to identify safer and more effective chemotherapies for Chagas disease.
Article
Pharmacology & Pharmacy
Morris Muliaditan, Oscar Della Pasqua
Summary: The study aims to develop a drug-disease model that distinguishes between drug- and system-specific properties, providing theoretical basis for the clinical application of anti-tubercular drugs.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Developmental Biology
Jesus Guerrero-Munoz, Lisvaneth Medina, Christian Castillo, Ana Liempi, Alejandro Fernandez-Moya, Sebastian Araneda, Yessica Ortega, Maura Rojas-Pirela, Juan Diego Maya, Ulrike Kemmerling
Summary: MiR-512-3p plays a critical role in parasite-induced apoptosis in trophoblast cells, as its inhibition effectively prevents the expression and enzymatic activity of caspase 3 and caspase 8. However, the inhibition of miR-512-3p does not completely prevent DNA fragmentation, indicating the involvement of other factors in this process. Furthermore, miR-512-3p may regulate the expression of Livin.
Article
Pharmacology & Pharmacy
Morris Muliaditan, Oscar Della Pasqua
Summary: This study introduced a drug-disease modeling framework for rational selection of doses and companion drugs in tuberculosis treatment. It was found that pyrazinamide could enhance the antibacterial activity of rifampicin and bedaquiline, while pretomanid and isoniazid had negative effects. This framework may help optimize combination therapies and improve treatment outcomes for tuberculosis.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Article
Veterinary Sciences
Lihua Yao, Lan Yang, Yuzhou Ling, Yanzhe Wei, Xiangguang Shen, Huanzhong Ding
Summary: This study evaluated the in vivo antibacterial activity of Tulathromycin against Actinobacillus pleuropneumoniae and determined the optimal dosage and usage of the drug using pharmacokinetic/pharmacodynamic relationships.
FRONTIERS IN VETERINARY SCIENCE
(2022)
Article
Agriculture, Dairy & Animal Science
Jiaxin Bao, Zhiyong Wu, Muhammad Ishfaq, Jian Wang, Yusong Miao, Dong Niu, Rui Li, Jichang Li, Chunli Chen
Summary: This study aimed to determine the relationship between the PK/PD index and efficacy of baicalin in the M. gallisepticum infection model in chickens. The results showed that baicalin concentration in lung tissues was higher than in plasma, and its ratios of AUC(24h)/MIC against bacteriostatic, bactericidal, and eradication were 0.62, 1.33, and 1.49 h, respectively. These findings provide potential reference for future clinical dose selection and evaluation of susceptibility breakpoints.
Article
Biochemistry & Molecular Biology
Ludmila F. de A. Fiuza, Denise G. J. Batista, Roberson D. Girao, Fabian Hulpia, Paula Finamore-Araujo, Mustafa M. Aldfer, Ehab Kotb Elmahallawy, Harry P. De Koning, Otacilio Moreira, Serge Van Calenbergh, Maria de Nazare C. Soeiro
Summary: Chagas disease, caused by Trypanosoma cruzi, is a serious public health problem without effective and safe treatment options. Nucleoside analogues, due to their different substrate specificities, show promise as a therapeutic alternative for Chagas disease. In this study, certain tubercidin derivatives were found to be highly potent and selective against T. cruzi, with their uptake mediated by the nucleoside transporter TcrNT2. These compounds effectively reduced parasitemia in cardiac cultures and showed no noticeable toxicity in mice. Further studies and combination evaluations are needed to identify more effective and safer therapies for Chagas disease.
Article
Infectious Diseases
Yasuhiro Umezaki, Kazuaki Matsumoto, Kazuro Ikawa, Yuta Yokoyama, Yuki Enoki, Akari Shigemi, Erika Watanabe, Koyo Nakamura, Keiichiro Ueno, Hideyuki Terazono, Norifumi Morikawa, Yasuo Takeda
Summary: This study demonstrated that the pharmacokinetic/pharmacodynamic index of pazufloxacin can be used to optimize dosing regimens for P. aeruginosa infection, and a successful PK/PD model was constructed.
Article
Pharmacology & Pharmacy
Daniel J. Blackwell, Abigail N. Smith, Tri Do, Aaron Gochman, Jeffrey Schmeckpeper, Corey R. Hopkins, Wendell S. Akers, Jeffrey N. Johnston, Bjorn C. Knollmann
Summary: This study developed a bioassay to measure the concentrations of nat-verticilide and ent-verticilide in murine plasma and correlated plasma concentrations with antiarrhythmic efficacy. The results showed that ent-verticilide has favorable pharmacokinetic properties and reduces ventricular arrhythmias in the nanomolar range, warranting further drug development.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2023)