Antiparasitic Effect of Stilbene and Terphenyl Compounds against Trypanosoma cruzi Parasites

AbstractBackgroundChagas disease, also known as American trypanosomiasis, is a potentially life-threatening illness caused by the protozoan parasite Trypanosoma cruzi. No progress in the treatment of this pathology has been made since Nifurtimox was introduced more than fifty years ago and is considered very aggressive and may cause several adverse effects. Currently, this drug has severe limitations, including high frequency of undesirable side effects and limited efficacy and availability and the research to discover new drugs for the treatment of Chagas disease is imperative. Many drugs available in the market are natural products as found in nature or compounds designed based on the str…

“Click” on PLGA-PEG and hyaluronic acid: Gaining access to anti-leishmanial pentamidine bioconjugates

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. Moreover, Pent has been encapsulated into PP nanoparticles by the oil-in-water emulsion method, with the aim to compare the biological activ…

Seroprevalence of and risk factors for Leishmania seropositivity in a sample population of Western Sicily (Italy)

Background: Leishmania is a vector-borne parasite responsible for significant morbidity and mortality worldwide. The aim of this study was to assess the prevalence of and risk factors for Leishmania infantum seropositivity in a sample of Sicilian population.Methods: A total of 260 subjects were interviewed using a standardized questionnaire and requested for an venous blood sample.Results: Overall, 36 subjects (13.8%) were seropositive against L. infantum with a statistically significant higher prevalence of positivity in older subjects (p=0.04). After adjustment for age, a higher risk for Leishmania seropositivity was found in subjects who had pets living outdoors and untreated with anti-p…

Effects of trans-stilbene and terphenyl compounds on different strains of Leishmania and on cytokines production from infected macrophages.

Most of the antileishmanial modern therapies are not satisfactory due to high toxicity or emergence of resistance and high cost of treatment. Previously, we observed that two compounds of a small library of trans-stilbene and terphenyl derivatives, ST18 and TR4, presented the best activity and safety profiles against Leishmania infantum promastigotes and amastigotes. In the present study we evaluated the effects of ST18 and the TR4 in 6 different species of Leishmania and the modifications induced by these two compounds in the production of 8 different cytokines from infected macrophages. We observed that TR4 was potently active in all Leishmania species tested in the study showing a leishm…

Genomic Analysis and Lineage Identification of SARS-CoV-2 Strains in Migrants Accessing Europe Through the Libyan Route

Many African countries, representing the origin of the majority of refugees, asylum-seekers, and other migrants, toward regions bordering on the Mediterranean area, are experiencing sustained local transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Sicily is one of the main entry gates of migrants crossing into Europe. We conducted a pilot study, based on the full-genome sequencing of SARS-CoV-2 strains isolated from migrants coming to Sicily by crossing the Mediterranean Sea, with the aim to investigate the viral genome polymorphism and to describe their genetic variations and the phylogenetic relationships. On June 21, a nongovernmental organization vessel rescu…

Antigen-specific T cells and cytokines detection as useful tool for understanding immunity against zoonotic infections.

Zoonoses include a broad range of diseases, that are becoming of great interest, due to the climate changing, that cause the adaptation of vectors to new niches and environments. Host immune responses play a crucial role in determining the outcome of infections, as documented by expansion of antigen-specific T cells during several zoonotic infections. Thus, understanding of the contribution of antigen-specific T-cell subsets in the host immune response is a powerful tool to evaluate the different immunological mechanisms involved in zoonotic infections and for the development of effective vaccines. In this paper we discuss the role of T cells in some eukaryotic and prokaryotic infectious mo…

Vascular patterns in cutaneous leishmaniasis: A videodermatoscopic study

Genetic tools discriminate strains of Leishmania infantum isolated from  humans and dogs in Sicily, Italy

Background Leishmaniasis is one of the most important vector-borne diseases and it represents a serious world health problem affecting millions of people. High levels of Leishmania infections, affecting both humans and animals, are recognized among Italian regions. Among these, Sicily has one of the highest prevalence of Leishmania infection. Methodology/Principal Findings Seventy-eight Leishmania strains isolated from human and animal samples across Sicily, were analyzed for the polymorphic k26-gene and genotypes were assigned according to the size of the PCR products. A multilocus microsatellite typing (MLMT) approach based on the analysis of 11 independent loci was used to investigate po…

First detection of SARS-CoV-2 A.23.1 sub-lineage in migrants arriving to Italy via the Mediterranean Sea and public health implications

Prion protein gene frequencies in three Sicilian dairy sheep populations

The objective of this paper was to investigate the prion protein (PrP) genotype and haplotype frequencies in three Sicilian dairy sheep populations. The three populations were: (1) 1096 Valle del Belice animals, (2) 1143 Comisana animals, and (3) 1771 individuals from 5 flocks with scrapie outbreaks, in which the animals were crossbreds derived from indigenous Sicilian dairy breeds. PrP genotypes are described for the three codons 136 (Alanine or Valine; A, V), 154 (Histidine or Arginine; H, R), and 171 (Glutamine, Arginine or Histidine; Q, R, H) which represent polymorphisms known to be linked with scrapie susceptibility. The Valle del Belice haplotype frequencies were 32.3% ARR, 6.5% AHQ,…

Ancient DNA polymorphisms analysis to investigate scrapie susceptibility in Sicilian sheep remains from medieval archaeological sites

Encephalopathy in sheep was at first described in Ireland in 1732 and was called “scrapie“ because the animals tend to tear their hair. Historically it seems to be the result of an incestuous union as breeding practice in old farms. In Sicily the animal bones found in association with the human skeletal remains from the tombs or city-sites, comprised a broad range of domestic. Usually, species included in the collected bones are domestic animals commonly eaten as sheep or goats, cattle, pigs, chickens and a small partridge. In this contest, the assemblage and the species identification is often difficult. Based on DNA barcoding, all the investigated bones were confirmed as belonging to the …

Asymptomatic Leishmania infantum/chagasi infection in blood donors of western Sicily.

The purpose of this study was to evaluate whether the risk of transfusion-transmitted visceral leishmaniasis was present in an area of western Sicily where the incidence of the disease is higher than the regional average. From May to December 2005, 1449 blood donors from Agrigento district (Sicily, Italy) were screened for the presence of anti-Leishmania antibodies by an indirect immunofluorescent antibody test (IFAT). Blood samples from IFAT-positive donors were examined by PCR to detect Leishmania DNA. Anti-Leishmania antibodies were found in 11 (0.75%) cases, among which Leishmania DNA was detected from four (36.4%). Particular techniques to inactivate different pathogens would be consid…

In vitro antileishmanial activity of trans-stilbene and terphenyl compounds

Leishmaniasis are globally widespread parasitic diseases which often leads to death if left untreated. Currently available drugs present different drawbacks, so there is an urgent need to develop new, safe and cost-effective drugs against leishmaniasis. In this study we tested a small library of trans-stilbene and terphenyl derivatives against promastigote, amastigotes and intramacrophage amastigote forms of Leishmania infantum. Two compounds of the series, the trans-stilbene 3 and the terphenyl 11, presented the best activity and safety profiles. Terphenyl 11 showed a leshmanicidal activity higher than pentostam and the ability to induce apoptosis selectively in Leishmania infantum while s…

ESAT-6 Peptide Recognition by Bovine CD8 + Lymphocytes of Naturally Infected Cows in Herds from Southern Italy

ABSTRACT The aim of this study was to define epitopes of Mycobacterium bovis from ESAT-6 (early secretory antigen of 6 kDa) recognized by CD8 + T lymphocytes from cows naturally infected with Mycobacterium bovis . We found that bovine CD8 + T cells recognized 10 out of 11 ESAT-6 peptides tested.

Effect of different salting technologies on the chemical and microbiological characteristics of PDO Pecorino Siciliano cheese

The present work was carried out to evaluate the effect of two salting technologies [dry salting (DS) and the combined dry-brine salting (DBS)] on the chemicophysical and microbiological characteristics of PDO Pecorino Siciliano cheeses of different final weight (6 and 12 kg). Dry matter was significantly influenced by both salting process and final size. Twelve kilogram cheeses treated by DBS showed higher protein content with higher soluble nitrogen per cent than 6 kg cheeses. Salt content was in the range 3.1–4.0% on dry matter. The colour did not show significant differences for any of the factors, but 12 kg cheeses subjected to DS showed higher yellow index than the other cheeses. The …

Exosome secretion by Leishmania infantum modulate the chemotactic behavior and cytokinic expression creating an environment permissive for early infection.

Abstract In recent years, several studies demonstrated the role of exosomes in intercellular communications, several Leishmania species belonging to subgenera Leishmania and Viannia have been demonstrated to release exosomes, and their role in parasite-macrophage interactions and in leishmaniasis development has been investigated. However, the release of exosomes by Leishmania infantum has not been studied so far. The aim of this study was to isolate and characterize L. infantum exosomes, and to investigate the biological activity of these exosomes in macrophage cultures. To this end, exosomes were collected from both amastigote and promastigote L. infantum conditioned medium by ultracentri…

Molecular characterization of dominant bacterial population in “Vastedda della Valle del Belice” cheese: preliminary investigation

The sensory characteristics of raw-milk cheeses are linked to the cheese-making process, to the environmental factors as animal feeding and to the biochemical and microbiological composition of the milk. In this report we temped to characterize the microflora in the typical Sicilian historical cheese as Vastedda della valle del Belice. Each cheese was previous subjected to microbial isolation on specific media (M17 and MRS). The colony obtained on the solid medium were subject to biochemical tests and DNA extraction. The microbial diversity occurring in the strains was evaluated by PCR, RFLP and sequencing targeted on 16S ribosomal DNA. A number of closest relatives species of lactic and co…

PrP Gene Polymorphism in Medieval Remains of Sicilian Sheep

Encephalopathy in sheep was at first described in Ireland in 1732 and was called scrapie. Ancient DNA in archaeogenetics represents an effective method to evaluate the ancestral pedigree of living animals and track evolutionary changes occurred between the past and the present day. Since several point mutations are today widely described in modern scrapie, no data about both sequence and frequency are still available for the prion protein (PrP) gene in ancient breeds. In order to evaluate whether the haplotypes distribution in ancient sheep differed from those of the modern population we evaluated polymorphism at four well know codons of the Prp Open Reading Frame. In the present work, we c…

Cryptic Leishmania infantum infection in Italian HIV infected patients.

Abstract Background Visceral leishmaniasis (VL) is a protozoan diseases caused in Europe by Leishmania (L.) infantum. Asymptomatic Leishmania infection is more frequent than clinically apparent disease. Among HIV infected patients the risk of clinical VL is increased due to immunosuppression, which can reactivate a latent infection. The aims of our study were to assess the prevalence of asymptomatic L. infantum infection in HIV infected patients and to study a possible correlation between Leishmania parasitemia and HIV infection markers. Methods One hundred and forty-five HIV infected patients were screened for the presence of anti-Leishmania antibodies and L. infantum DNA in peripheral blo…