Publications

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94 Publications visible to you, out of a total of 94
Impact of pulmonary African trypanosomes on the immunology and function of the lung.

Abstract (Expand)

Approximately 20% of sleeping sickness patients exhibit respiratory complications, however, with a largely unknown role of the parasite. Here we show that tsetse fly-transmitted Trypanosoma brucei … parasites rapidly and permanently colonize the lungs and occupy the extravascular spaces surrounding the blood vessels of the alveoli and bronchi. They are present as nests of multiplying parasites exhibiting close interactions with collagen and active secretion of extracellular vesicles. The local immune response shows a substantial increase of monocytes, macrophages, dendritic cells and gammadelta and activated alphabeta T cells and a later influx of neutrophils. Interestingly, parasite presence results in a significant reduction of B cells, eosinophils and natural killer cells. T. brucei infected mice show no infection-associated pulmonary dysfunction, mirroring the limited pulmonary clinical complications during sleeping sickness. However, the substantial reduction of the various immune cells may render individuals more susceptible to opportunistic infections, as evident by a co-infection experiment with respiratory syncytial virus. Collectively, these observations provide insights into a largely overlooked target organ, and may trigger new diagnostic and supportive therapeutic approaches for sleeping sickness.

Authors: D. Mabille, L. Dirkx, S. Thys, M. Vermeersch, D. Montenye, M. Govaerts, S. Hendrickx, P. Takac, J. Van Weyenbergh, I. Pintelon, P. Delputte, L. Maes, D. Perez-Morga, J. P. Timmermans, G. Caljon

Date Published: 18th Nov 2022

Publication Type: Journal Article

Nanoassemblies from Amphiphilic Sb Complexes Target Infection Sites in Models of Visceral and Cutaneous Leishmaniases

Abstract (Expand)

This work aims to evaluate whether nanoassemblies (NanoSb) made from antimony(V) complexes with octanoyl-N-methylglucamide (SbL8) or decanoyl-N-methylglucamide (SbL10) would effectively target the … infection sites in visceral and cutaneous leishmaniases (VL and CL). NanoSb were investigated regarding stability at different pHs, accumulation of Sb in the macrophage host cell and liver, and in vitro and in vivo activities in models of leishmaniasis. The kinetic stability assay showed that NanoSb are stable at neutral pH, but release incorporated lipophilic substance after conformational change in media that mimic the gastric fluid and the parasitophorous vacuole. NanoSb promoted greater accumulation of Sb in macrophages and in the liver of mice after parenteral administration, when compared to conventional antimonial Glucantime®. SbL10 was much more active than Glucantime® against intramacrophage Leishmania amastigotes and less cytotoxic than SbL8 against macrophages. The in vitro SbL10 activity was further enhanced with co-incorporated miltefosine. NanoSb showed high antileishmanial activity in the L. donovani murine VL after parenteral administration and moderate activity in the L. amazonensis murine CL after topical treatment. This study supports the ability of NanoSb to effectively deliver a combination of Sb and co-incorporated drug to host cell and infected tissues, in a better way than Glucantime® does.

Authors: Juliane S. Lanza, Virginia M. R. Vallejos, Guilherme S. Ramos, Ana Carolina B. de Oliveira, Cynthia Demicheli, Luis Rivas, Sébastien Pomel, Philippe M. Loiseau, Frédéric Frézard

Date Published: 21st Aug 2022

Publication Type: Journal Article

Current Treatments to Control African Trypanosomiasis and One Health Perspective

Abstract (Expand)

Human African Trypanosomiasis (HAT, sleeping sickness) and Animal African Trypanosomiasis (AAT) are neglected tropical diseases generally caused by the same etiological agent, Trypanosoma brucei. Despite … important advances in the reduction or disappearance of HAT cases, AAT represents a risky reservoir of the infections. There is a strong need to control AAT, as is claimed by the European Commission in a recent document on the reservation of antimicrobials for human use. Control of AAT is considered part of the One Health approach established by the FAO program against African Trypanosomiasis. Under the umbrella of the One Health concepts, in this work, by analyzing the pharmacological properties of the therapeutic options against Trypanosoma brucei spp., we underline the need for clearer and more defined guidelines in the employment of drugs designed for HAT and AAT. Essential requirements are addressed to meet the challenge of drug use and drug resistance development. This approach shall avoid inter-species cross-resistance phenomena and retain drugs therapeutic activity.

Authors: Alberto Venturelli, Lorenzo Tagliazucchi, Clara Lima, Federica Venuti, Giulia Malpezzi, George E. Magoulas, Nuno Santarem, Theodora Calogeropoulou, Anabela Cordeiro-da-Silva, Maria Paola Costi

Date Published: 27th Jun 2022

Publication Type: Journal Article

4-Amino-1,8-naphthalimide–ferrocene conjugates as potential multi-targeted anticancer and fluorescent cellular imaging agents

Abstract

Eight ferrocenyl 4-amino-1,8-naphthalimide logic gates for acidity and oxidisability are repurposed as anti-proliferation and cellular imaging agents against MCF-7 and K562 cancer cell lines.

Authors: Alex D. Johnson, Joseph A. Buhagiar, David C. Magri

Date Published: 15th Dec 2021

Publication Type: Journal Article

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