Search results for "Mania"

Cathepsin B in Antigen-Presenting Cells Controls Mediators of the Th1 Immune Response during Leishmania major Infection

2014

Resistance and susceptibility to Leishmania major infection in the murine model is determined by the capacity of the host to mount either a protective Th1 response or a Th2 response associated with disease progression. Previous reports involving the use of cysteine cathepsin inhibitors indicated that cathepsins B (Ctsb) and L (Ctsl) play important roles in Th1/Th2 polarization during L. major infection in both susceptible and resistant mouse strains. Although it was hypothesized that these effects are a consequence of differential patterns of antigen processing, the mechanisms underlying these differences were not further investigated. Given the pivotal roles that dendritic cells and macrop…

Ensemble-based ADME-Tox profiling and virtual screening for the discovery of new inhibitors of the Leishmania mexicana cysteine protease CPB2.8ΔCTE

2018

Abstract: In an effort to identify novel molecular warheads able to inhibit Leishmania mexicana cysteine protease CPB2.8CTE, fused benzo[b]thiophenes and ,'-triketones emerged as covalent inhibitors binding the active site cysteine residue. Enzymatic screening showed a moderate-to-excellent activity (12%-90% inhibition of the target enzyme at 20m). The most promising compounds were selected for further profiling including in vitro cell-based assays and docking studies. Computational data suggest that benzo[b]thiophenes act immediately as non-covalent inhibitors and then as irreversible covalent inhibitors, whereas a reversible covalent mechanism emerged for the 1,3,3'-triketones with a Y-to…

Triazolopyridyl ketones as a novel class of antileishmanial agents. DNA binding and BSA interaction

2014

A new series of triazolopyridyl pyridyl ketones has been synthetized by regioselective lithiation of the corresponding [1,2,3]triazolo[1,5-a]pyridine at 7 position followed by reaction with different electrophiles. The in vitro antileishmanial activity of these compounds was evaluated against Leishmaniainfantum, Leishmaniabraziliensis, Leishmaniaguyanensis and Leishmaniaamazonensis. Compounds 6 and 7 were found to be the most active leishmanicidal agents. Both of them showed activities at micromolar concentration against cultured promastigotes of Leishmania spp. (IC₅₀=99.8-26.8 μM), without cytotoxicity on J774 macrophage cells. These two compounds were also tested in vivo in a murine model…

Requirements for Th1-dependent immunity against infection with Leishmania major

2004

Protective immunity against cutaneous leishmaniasis is dependent on the induction of Th1/Tc1 immune responses resulting in efficient parasite elimination. In this review, the mechanisms leading to protection are discussed with special focus on the role of Leishmania major-infected dendritic cells (DC) in induction of Th1-dependent immunity. Murine strain-dependent differences between DC derived from Leishmania-susceptible as compared to resistant mice are highlighted.

Research in practice: Different dendritic cell types in skin with various functions - important implications for intradermal vaccines

2011

Summary It was long believed that epidermal Langerhans cells (LC) are responsible for the initiation of cellular immunity. Only recently it has been shown that in skin alone 5 different subtypes of dendritic cells (DC) can be identified. Among these, LC, but also two Langerin-expressing dermal DC populations and two more Langerin-negative DC subtypes exist. Novel findings in the model disease leishmaniasis, as well as evidence from research in contact hypersensitivity, have revealed that activation of LC in skin leads to induction of regulatory, immunosuppressive T cells, whereas the other skin DC subtypes stimulate effector T cells. Thus, when producing vaccines designed for intradermal us…

The Caribbean Plateau and OAE2: Resolution of timing and trace metal release

2013

Venezuela's humanitarian crisis, resurgence of vector-borne diseases, and implications for spillover in the region

2019

In the past 5–10 years, Venezuela has faced a severe economic crisis, precipitated by political instability and declining oil revenue. Public health provision has been affected particularly. In this Review, we assess the impact of Venezuela's health-care crisis on vector-borne diseases, and the spillover into neighbouring countries. Between 2000 and 2015, Venezuela witnessed a 359% increase in malaria cases, followed by a 71% increase in 2017 (411 586 cases) compared with 2016 (240 613). Neighbouring countries, such as Brazil, have reported an escalating trend of imported malaria cases from Venezuela, from 1538 in 2014 to 3129 in 2017. In Venezuela, active Chagas disease transmission has be…

Promising trypanocidal heterocyclic compounds of natural origin and their synthetic analogs

2019

Abstract Diseases caused by members of the order Trypanosomatidae include human African trypanosomiasis (HAT) and Chagas disease, caused by species of Trypanosoma brucei and Trypanosoma cruzi, respectively, as well as leishmaniasis, caused by various species of Leishmania spp. These infections belong to the so-called neglected tropical diseases group, which are a diverse group of communicable diseases that prevail in tropical and subtropical conditions in 149 countries and affect more than one billion people in addition to costing developing economies billions of dollars every year. The available pharmacotherapies for combatting these diseases are limited and associated with strong side eff…

Cytotoxicity and antileishmanial activity of Annona muricata pericarp

2000

Abstract Hexane, ethyl acetate and methanol extracts of Annona muricata pericarp were tested in vitro against Leishmania braziliensis and L. panamensis promastigotes, and against cell line U-937. The ethyl acetate extract was more active than the other extracts and even of Glucantime® used as reference substance. Its fractionation led to the isolation of three acetogenins — annonacin, annonacin A and annomuricin A.

Physical, Psychological and Sexual Abuse of the Minor in the Families from the Northwestern Region of Romania- Social and Medical Forensics

2020

Background: In Romania, the abuse within the family of the minor child is a widespread phenomenon, its extent is insufficiently known because of ignorance/not reporting all the existing cases.
 Methods: The participants of the research are represented by two independent groups from the NW Romania 2007-2011, one for sociological study (1544 parents and 1283 children) and another for forensic statistical study (2761 cases of abused children). The sociological study was carried out by analyzing questionnaires applied in schools located in Bihor County, both to children and parents. The statistical analysis was carried out by studying the cases of the physically, sexually, and psychologica…