Article
Pharmacology & Pharmacy
Lais Alonso, Sebastiao Antonio Mendanha, Rodrigo Saar Gomes, Miriam Leandro Dorta, Antonio Alonso
Summary: The study using EPR spectroscopy investigated the interactions of AmB and MIL with cell membranes of various cells, revealing higher affinity of AmB for Leishmania parasites and a more localized effect on the membrane. This suggests that the antiproliferative and cytotoxic effects of these drugs are associated with changes in cell membranes.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Antu Das, Junaid Jibran Jawed, Manash C. Das, Shabina Parveen, Chinmoy Ghosh, Subrata Majumdar, Bhaskar Saha, Surajit Bhattacharjee
Summary: The combination of sub-optimal doses of lupeol and AmpB significantly reduces parasitic burden in the liver and spleen and enhances immune modulation effects in L. donovani-infected mice. This combination also increases nitric oxide production, suppresses Th2 cytokine production, and reduces phosphorylation of extracellular signal-related kinase.
Article
Chemistry, Medicinal
Omar Casanova-Alvarez, Aliuska Morales-Helguera, Miguel Angel Cabrera-Perez, Reinaldo Molina-Ruiz, Christophe Molina
Summary: In this study, an automated workflow was developed for predicting antileishmanial activity, utilizing a large, diverse, and highly imbalanced dataset of compounds. The workflow implemented a novel strategy based on balanced training sets and a consensus model using decision trees, resulting in improved predictive accuracy for the test and external sets when compared to other base models like Gaussian-Naive-Bayes and Support-Vector-Machine. The consensus model was found to be effective in prioritizing active compounds with high prediction sensitivity, demonstrating the importance of this approach in QSAR problems.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Parasitology
Chonlada Mano, Aphisek Kongkaew, Pongsri Tippawangkosol, Anuluck Junkum, Padet Siriyasatien, Narissara Jariyapan
Summary: This study reveals the resistance of Leishmania martiniquensis to amphotericin B deoxycholate (AmpB) and miltefosine (MIL), and suggests further research into the mechanisms of this resistance and the development of effective methods to identify drug-resistant parasites.
PARASITOLOGY RESEARCH
(2023)
Article
Infectious Diseases
Andrew A. Voak, Andy Harris, Jose Miguel Coteron-Lopez, Inigo Angulo-Barturen, Santiago Ferrer-Bazaga, Simon L. Croft, Karin Seifert
Summary: This study characterized the pharmacokinetic and pharmacodynamic properties of anti-leishmanial drugs AmBisome and miltefosine in a mouse model of visceral leishmaniasis. Optimal dosing strategies for AmBisome were proposed, demonstrating a wider therapeutic range compared to miltefosine. The study also highlighted the importance of using animal models in drug development for visceral leishmaniasis.
PLOS NEGLECTED TROPICAL DISEASES
(2021)
Editorial Material
Public, Environmental & Occupational Health
Begona Monge-Maillo, Francesca F. Norman, Sandra Chamorro-Tojeiro, Francesca Gioia, Jose-Antonio Perez-Molina, Carmen Chicharro, Javier Moreno, Rogelio Lopez-Velez
Summary: Post-kala-azar dermal leishmaniasis caused by Leishmania infantum in an HIV-negative patient is rare, and this case highlights its association with other types of immunosuppression. In addition, this case report presents an effective therapeutic option with miltefosine, which can be very useful due to limited reported experience.
JOURNAL OF TRAVEL MEDICINE
(2022)
Article
Immunology
Sakib Burza, Raman Mahajan, Shahwar Kazmi, Neal Alexander, Deepak Kumar, Vikash Kumar, Estrella Lasry, Amit Harshana, Alan de Lima Pereira, Pradeep Das, Neena Verma, Vidya Nand Ravi Das, Chandra Shekhar Lal, Bharat Rewari, Vishal Goyal, Suman Rijal, Fabiana Alves, Naresh Gill, Krishna Pandey
Summary: This study conducted in a hospital in India compared two different treatment regimens for 150 patients with HIV and VL. The results showed that combination therapy is safe, well-tolerated, effective, and reduces treatment duration.
CLINICAL INFECTIOUS DISEASES
(2022)
Article
Instruments & Instrumentation
Lipika Ray, R. Karthik, Vikas Shrivastava, Sheelendra Pratap Singh, A. B. Pant, Neena Goyal, Kailash C. Gupta
Summary: A nanoformulation of AmB and Pip was developed, with controlled release properties and protection from acidic pH, showing enhanced drug bioavailability, non-nephrotoxic nature, and potential antileishmanial activity up to 96% inhibition of the parasite in vivo in the golden hamster-L. donovani model.
DRUG DELIVERY AND TRANSLATIONAL RESEARCH
(2021)
Review
Parasitology
Malgorzata Anna Domagalska, Michael P. Barrett, Jean-Claude Dujardin
Summary: Treatment failure (TF), particularly in leishmaniasis, is a major concern in the management of parasitic diseases. It is unclear whether drug resistance (DR), measured by in vitro drug susceptibility assays, is the sole contributor to TF. This article addresses three key questions to clarify the relationship between TF and DR.
TRENDS IN PARASITOLOGY
(2023)
Review
Parasitology
Herve Lecoeur, Eric Prina, Maria Gutierrez-Sanchez, Gerald F. Spaeth
Summary: Intracellular parasites have evolved complex strategies to disrupt host cell functions and ensure their own survival. Leishmania parasites, in particular, cause severe immunopathologies by thriving inside immune cells. While the impact of Leishmania infection on host cell phenotype and functions has been studied, the regulatory mechanisms underlying host cell subversion were only recently investigated.
TRENDS IN PARASITOLOGY
(2022)
Article
Parasitology
Camila S. Freitas, Joao A. Oliveira-da-Silva, Daniela P. Lage, Rafaella R. Costa, Debora V. C. Mendonca, Vivian T. Martins, Thiago A. R. Reis, Luciana M. R. Antinarelli, Amanda S. Machado, Grasiele S. V. Tavares, Fernanda F. Ramos, Vinicio T. S. Coelho, Rory C. F. Brito, Fernanda Ludolf, Miguel A. Chavez-Fumagalli, Bruno M. Roatt, Gabriela S. Ramos, Jennifer Munkert, Flaviano M. Ottoni, Priscilla R. V. Campana, Maria V. Humbert, Elaine S. Coimbra, Fernao C. Braga, Rodrigo M. Padua, Eduardo A. F. Coelho
Summary: Treatment for visceral leishmaniasis is challenging due to drug toxicity, high cost, and parasite resistance. In this study, the use of the cardenolide digitoxigenin (DIGI) from Digitalis lanata leaves showed promising antileishmanial activity against Leishmania infantum, with potential as a therapeutic agent. Formulation of DIGI in polymeric micelles improved its efficacy in reducing parasite load and inducing an immune response in infected mice, outperforming the current control drug miltefosine. Future studies on DIGI as a treatment for VL are warranted.
PARASITOLOGY RESEARCH
(2021)
Article
Parasitology
Bianca A. Ferreira, Elizabeth M. Coser, Cristiele Saborito, Edite H. Yamashiro-Kanashiro, Adriano C. Coelho, Jose Angelo L. Lindose
Summary: There are at least seven Leishmania species in Brazil that cause tegumentary leishmaniasis. The current treatment options have limitations and side effects. This study investigated the susceptibility of these parasites to two drugs and found moderate variation in their sensitivity.
EXPERIMENTAL PARASITOLOGY
(2023)
Article
Infectious Diseases
Ana Isabel Olias-Molero, Pedro Botias, Montserrat Cuquerella, Jesus Garcia-Cantalejo, Emilia Barcia, Susana Torrado, Juan Jose Torrado, Jose Maria Alunda
Summary: This study investigated the impact of clindamycin on the intestinal microbiome and the availability and distribution of miltefosine in target organs. It was found that clindamycin significantly altered the relative abundance of the intestinal microbiome, but had no clear effect on the availability of miltefosine.
Article
Infectious Diseases
Kerstin K. Rauwolf, Caroline Hoertnagl, Cornelia Lass-Floerl, Andreas H. Groll
Summary: In vitro analysis showed that adding porcine surfactant up to a concentration of 10% had minimal impact on the activity of antifungal agents used for prophylaxis and treatment of invasive pulmonary aspergillosis.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2022)
Article
Multidisciplinary Sciences
Devki Nandan, Eleanor Chen, Fabian Chang, Kyung-Mee Moon, Leonard J. Foster, Neil Reiner
Summary: Recently, autophagy has been found to play a role in host defense against intracellular pathogens, but some pathogens, like Leishmania, can manipulate the host's autophagy to survive. Our study showed that Leishmania induces non-classical autophagy in infected macrophages, independently of mammalian target of rapamycin complex 1 regulation, suggesting the modulation of autophagy to enhance parasite survival.
Article
Pediatrics
Timothy H. Ciesielski, Xueyi Zhang, Alessandra Tacconelli, Irja Lutsar, Vincent Meiffredy de Cabre, Emmanuel Roilides, Cinzia Ciccacci, Paola Borgiani, William K. Scott, Scott M. Williams, Giorgio Sirugo
Summary: Late-onset neonatal sepsis (LOS) is a rare and severe condition with high mortality rates. This study aimed to identify genetic variants associated with LOS. The results showed that genetic susceptibility to LOS is sexually dimorphic and NOTCH signaling plays a role in determining risk. There were also sex-specific associations between genes and sepsis, highlighting the importance of sex-specific treatment strategies.
PEDIATRIC RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Wen Yao Mak, Qing Xi Ooi, Cintia Valeria Cruz, Irene Looi, Kah Hay Yuen, Joseph F. Standing
Summary: This study utilized nlmixr to model the pharmacokinetic data of metformin and compared the performances of SAEM and FOCEi in terms of bias, precision, and robustness to initial estimates for parameter estimation. The results showed that SAEM outperformed FOCEi in these aspects.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Editorial Material
Infectious Diseases
Joseph F. Standing, Akosua Adom Agyeman
LANCET INFECTIOUS DISEASES
(2023)
Article
Pediatrics
Sandra Walsh, Shan Pan, Yucheng Sheng, Frank Kloprogge, Joe F. Standing, Brian J. Anderson, Padmanabhan Ramnarayan
Summary: In this study, a PKPD model for salbutamol in pediatric patients was developed. The results showed that an infusion of 0.5 μg/kg/min after bolus achieves effective bronchodilation, but higher infusion rates are associated with increased tachycardia and hyperglycemia.
ARCHIVES OF DISEASE IN CHILDHOOD
(2023)
Editorial Material
Pharmacology & Pharmacy
Joseph F. Standing
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Infectious Diseases
Japhette E. Kembou-Ringert, John Readman, Claire M. Smith, Judith Breuer, Joseph F. Standing
Summary: Conventional cell culture systems involve growing cells in stationary cultures, which does not reflect normal physiological conditions. Hollow-fibre bioreactors have been developed to overcome these limitations and have been widely used in various fields. This review focuses on the usage of these bioreactors in viral infection studies and highlights their potential applications in vaccine development and antiviral resistance mechanisms.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2023)
Article
Medicine, General & Internal
Christopher C. Butler, F. D. Richard Hobbs, Oghenekome A. Gbinigie, Najib M. Rahman, Gail Hayward, Duncan B. Richards, Jienchi Dorward, David M. Lowe, Joseph F. Standing, Judith Breuer, Saye Khoo, Stavros Petrou, Kerenza Hood, Jonathan S. Nguyen-Van-Tam, Mahendra G. Patel, Benjamin R. Saville, Joe Marion, Emma Ogburn, Julie Allen, Heather Rutter, Nick Francis, Nicholas P. B. Thomas, Philip Evans, Melissa Dobson, Tracie-Ann Madden, Jane Holmes, Victoria Harris, May Ee Png, Mark Lown, Oliver van Hecke, Michelle A. Detry, Christina T. Saunders, Mark Fitzgerald, Nicholas S. Berry, Lazaro Mwandigha, Ushma Galal, Sam Mort, Bhautesh D. Jani, Nigel D. Hart, Haroon Ahmed, Daniel Butler, Micheal McKenna, Jem Chalk, Layla Lavallee, Elizabeth Hadley, Lucy Cureton, Magdalena Benysek, Monique Andersson, Maria Coates, Sarah Barrett, Clare Bateman, Jennifer C. Davies, Ivy Raymundo-Wood, Andrew Ustianowski, Andrew Carson-Stevens, Ly-Mee Yu, Paul Little
Summary: This study aimed to determine the safety, effectiveness, and cost-effectiveness of molnupiravir in vaccinated high-risk patients in the community. The results showed that molnupiravir did not reduce hospital admissions or deaths associated with COVID-19 compared to usual care in this population.
Article
Medicine, General & Internal
Joao Malato, Luis Graca, Nuno Sepulveda
Summary: Misdiagnosis of ME/CFS can be caused by different case definitions or failure to diagnose other diseases, leading to difficulties in reproducing research findings. Simulated data showed that studies with over 500 individuals per group have a minimum power of 80% to detect a genuine association. However, in studies where the potential causal factor is not perfectly determined, such as serological association studies, a minimum power of 80% can only be achieved with over 1000 individuals per group.
Article
Infectious Diseases
J. B. Readman, M. Acman, A. Hamawandi, Cheng-Hsun Chiu, M. Sharland, J. A. Lindsay, J. F. Standing
Summary: In neonatal ICUs, ubiquitous infection with ESBL-producing Enterobacteriaceae is a major concern due to increasing antibiotic resistance. Distinguishing between bacterial and viral sepsis often leads to empirical antibiotics being used, contributing to resistance. Through testing, it was found that combining cefotaxime or ampicillin with sulbactam and gentamicin effectively inhibits the growth of ESBL-producing isolates and clears the infection. This combination showed consistent bactericidal activity at clinically achievable concentrations.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2023)
Review
Anesthesiology
Maddlie Bardol, Shan Pan, Suellen M. Walker, Joseph F. Standing, Joy M. Dawes
Summary: Pharmacokinetic pharmacodynamic modeling is a valuable tool for understanding the relationship between drug concentration and effect, particularly in pediatric patients. It helps to identify variability among patients and adjust dosing for optimal pain management. Consideration of size and maturation is crucial in accurate modeling and determining optimal dose in different age groups. However, assessing analgesic and sedative effects in children can be challenging due to the multidimensional nature of pain and limitations of measurement tools.
PEDIATRIC ANESTHESIA
(2023)
Editorial Material
Medicine, General & Internal
Eric William Rogier, Emanuele Giorgi, Kevin Tetteh, Nuno Sepulveda
FRONTIERS IN MEDICINE
(2023)
Article
Veterinary Sciences
Ines Cunha Machado, Telmo Nunes, Miguel Maximino, Joao Malato, Luis Tavares, Virgilio Almeida, Nuno Sepulveda, Solange Gil
Summary: By creating infectious disease surveillance systems, routine collection and analysis of clinical data can contribute to an epidemiologic control of infectious diseases. The Biological Isolation and Containment Unit of the Faculty of Veterinary Medicine, University of Lisbon, has a database for collecting data on pets with infectious diseases. This study aims to identify the main dog infectious diseases over a 7-year period and analyze potential risk factors. The most frequent diagnoses were parvovirosis, leptospirosis, multidrug-resistant bacterial infections, and distemper.
VETERINARY SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Aswin Anand Pai, Ezhilpavai Mohanan, John C. Panetta, Uday P. Kulkarni, Raveen Stephen Stallon Illangeswaran, Balaji Balakrishnan, Agila Jayaraman, Eunice S. Edison, Kavitha M. Lakshmi, Anup J. Devasia, Nambiathayil Aboobacker Fouzia, Anu Korula, Aby Abraham, Biju George, Alok Srivastava, Vikram Mathews, Joseph F. Standing, Poonkuzhali Balasubramanian
Summary: A new chemotherapy regimen has significantly improved hematopoietic stem cell transplantation outcomes for patients with high-risk beta-thalassemia major, but complications still exist. A study on the dose-exposure-response relationship of treosulfan reveals that lower exposure increases the risk of graft rejection and early transplant-related mortality. Therapeutic drug monitoring-based dose adjustment may be beneficial.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Anna D. Grabowska, Mateusz Watroba, Joanna Witkowska, Agnieszka Mikulska, Nuno Sepulveda, Dariusz Szukiewicz
Summary: The blood-brain barrier (BBB) plays a crucial role in regulating the flow of substances between the blood and the central nervous system. Disruption of the BBB due to imbalanced blood glucose levels can lead to neuroinflammation and increase the risk of neurodegenerative diseases. Resveratrol (RSV), a natural compound with anti-diabetic, anti-inflammatory, and neuroprotective properties, activates SIRT1, a key regulator of metabolism. This study aimed to assess the response of astrocyte SIRT1 to neuroinflammation and RSV treatment in different glycemic backgrounds. The results showed that abnormal glycemic states had a worse prognosis for RSV therapy effectiveness compared to normoglycemia.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Infectious Diseases
Charlotte I. S. Barker, Karin Kipper, Dagan O. Lonsdale, Kirstie Wright, Georgina Thompson, Min Kim, Mark A. Turner, Atholl Johnston, Mike Sharland, Joseph F. Standing, NAPPA Study Consortium
Summary: The Neonatal and Paediatric Pharmacokinetics of Antimicrobials study aimed to characterize the pharmacokinetic profiles of commonly used penicillins in paediatric patients and provide evidence-based dosing recommendations for future use. The study analyzed data obtained during routine care and used model-based simulations to test dosing regimens.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2023)
