196 research outputs found
Perspectives on polymeric nanostructures for the therapeutic application of antimicrobial peptides
Antimicrobial peptides (AMPs) are a class of promising anti-infective molecules but
their therapeutic application is opposed by their poor bioavailability, susceptibility to
protease degradation and potential toxicity. The advancement of nanoformulation
technologies offers encouraging perspectives for the development of novel
therapeutic strategies based on AMPs to treat antibiotic resistant microbial infections.
Additionally, the use of polymers endowed per-se with antibacterial properties,
stands out as an innovative approach for the development of a new generation of
drug delivery systems in which an enhanced antimicrobial action could be obtained by
the synergic combination of bioactive polymer matrices and drugs. Herein, the latest
AMPs drug delivery research is discussed
Detection and characterization of Rickettsial strains in ticks from Sardinia, Italy
The aim of this study was, firstly, to detect the presence of Rickettsial DNA by PCR and, then, to identify
the Rickettsiae species using restriction endonuclease fragment length polymorphism (RFLP) on two amplified
genes
Investigation into Cryptosporidium and Giardia in bivalve mollusks farmed in Sardinia region and destined for human consumption
Cryptosporidium and Giardia are protozoan parasites transmitted by fecal-oral ingestion of (oo)cysts, and are responsible for enteritis in several animal species and humans worldwide. These (oo)cysts can survive for over a year in aquatic environments and can accumulate in bivalve mollusks, which filter large volumes of water. The aim of this study is to evaluate the natural occurrence of Cryptosporidium and Giardia contamination in different specimens of edible bivalves mollusks from farming sites of the western and north-eastern coasts of Sardinia. From April 2011 to February 2012, 1095 specimens of Mytilus galloprovincialis and 240 of Crassostrea gigas were sampled from Olbia and Oristano gulf and San Teodoro pond. Hepatopancreas and gills, including the labial palp, were examined for oocysts and cysts after pooling and homogenisation using different techniques: i) staining for light and fluorescence microscopy; ii) direct immunofluorescence (IF) Merifluor® test Cryptosporidium/ Giardia (Meridian Bioscience Inc., Cincinnati, OH, USA); and iii) molecular procedures. However, in the context under study, all mollusks examined with the three main diagnostic techniques were negative for both parasites pointing out the hypothetically low zoonotic risk related to Cryptosporidium and Giardia in bivalves, especially Mytilus galloprovincialis and Crassostrea gigas
Preparazione di derivati azotati di bifenili di origine naturale da utilizzare come leganti per siti nicotinici
I recettori nicotinici sono canali ionici attivati da un legante e costituiscono le
molecole chiave che mediano la trasmissione tra un neurone e l’altro attraverso
l’acetilcolina. Essi sono coinvolti nella malattia dell’Alzheimer, pertanto, al fine di
contrastare gli effetti della patologia, si somministrano al malato farmaci che aumentano la
produzione di acetilcolina, sostanza che, a sua volta, potenzia i recettori nicotinici. Si pensa,
inoltre, che questi recettori possano arrestare la morte cellulare, favorendo quindi non solo
un recupero funzionale, ma anche un rallentamento della malattia.
Una parte della nostra ricerca propone la rivisitazione di strutture di leganti già note
per questa patologia, soprattutto di origine naturale, con l’inserimento di unitÃ
atropisomeriche di tipo bifenilico nella molecola al fine di migliorare i requisiti sterici,
elettronici, capacità ossidanti e biocompatibilità richiesti dal legante
differential effects of voluntary ethanol consumption on dopamine output in the nucleus accumbens shell of roman high and low avoidance rats a behavioral and brain microdialysis study
The Roman high(RHA) and low-Avoidance (RLA) rats were selectively bred for rapid vs poor acquisition of two-way active avoidance behavior. These lines differ in numerous behavioral traits, with RLA rats being more fearful/anxious than RHA rats, and the latter being novelty-seekers and showing larger intake of, and preference for, addictive substances including ethanol (ETH). Moreover, several differences in central dopaminergic, serotonergic, and GABAergic functions have been reported in these two lines. Since those neural systems are involved in the regulation of ETH consumption, it was considered of interest to investigate: 1) the differences in ETH intake and preference between RHA and RLA rats, 2) the effects of ETH on DA release in the shell of the nucleus accumbens (AcbSh) using brain microdialysis. ETH solutions of increasing concentrations (2% - 10%) were presented on alternate days in a free choice with water. To examine ETH intake and preference stability, animals were subsequently switched to daily presentations of 10% ETH for 10 consecutive days. RHA rats consumed significantly larger amounts of ETH and displayed higher ETH preference than did RLA rats throughout the acquisition and maintenance phases. Following chronic exposure to ETH the animals were habituated to a restricted access to ETH schedule (2% ETH, 2 h per day × 4 days) before surgical implantation of a dialysis probe in the AcbSh. Under these experimental conditions, voluntary ETH intake (2%, 1 h, p.o.) produced a significant increase in accumbal DA output in RHA rats but not in their RLA counterparts. Finally, the i.p. administration of ETH (0.25 g/kg) to na?ve Roman rats produced a significant increment in accumbal DA output only in RHA rats. These results indicate that the mesolimbic dopaminergic system of RHA rats is more responsive to the effects of ETH than that of RLA rats
Chitosan nanoparticles loaded with the antimicrobial peptide temporin B exert a long-term antibacterial activity in vitro against clinical isolates of Staphylococcus epidermidis
Nowadays, the alarming rise in multidrug-resistant microorganisms urgently demands for suitable alternatives to current antibiotics. In this regard, antimicrobial peptides (AMPs) have received growing interest due to their broad spectrum of activities, potent antimicrobial properties, unique mechanisms of action, and low tendency to induce resistance. However, their pharmaceutical development is hampered by potential toxicity, relatively low stability and manufacturing costs. In the present study, we tested the hypothesis that the encapsulation of the frog-skin derived AMP temporin B (TB) into chitosan nanoparticles (CS-NPs) could increase peptide's antibacterial activity, while reducing its toxic potential. TB-loaded CS-NPs with good dimensional features were prepared, based on the ionotropic gelation between CS and sodium tripolyphosphate. The encapsulation efficiency of TB in the formulation was up to 75%. Release kinetic studies highlighted a linear release of the peptide from the nanocarrier, in the adopted experimental conditions. Interestingly, the encapsulation of TB in CS-NPs demonstrated to reduce significantly the peptide's cytotoxicity against mammalian cells. Additionally, the nanocarrier evidenced a sustained antibacterial action against various strains of Staphylococcus epidermidis for at least 4 days, with up to 4-log reduction in the number of viable bacteria compared to plain CS-NPs at the end of the observational period. Of note, the antimicrobial evaluation tests demonstrated that while the intrinsic antimicrobial activity of CS ensured a "burst" effect, the gradual release of TB further reduced the viable bacterial count, preventing the regrowth of the residual cells and ensuring a long-lasting antibacterial effect. The developed nanocarrier is eligible for the administration of several AMPs of therapeutic interest with physical-chemical characteristics analog to those of TB
Rheumatoid arthritis patient antibodies highly recognize IL-2 in the immune response pathway involving IRF5 and EBV antigens
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by a progressive joint damage due to largely unknown environmental factors acting in concert with risk alleles conferring genetic susceptibility. A major role has been attributed to viral infections that include past contacts with Epstein-Barr virus (EBV) and, more recently, to non-protein coding sequences of human endogenous retrovirus K (HERV-K) integrated in the human genome. Molecular mimicry between viral and self proteins is supposed to cause the loss of immune tolerance in predisposed hosts. There are evidences that anti-IL-2 antibodies (Abs) are present in subjects affected by autoimmune diseases and may be responsible for alterations in regulatory T cell responses. In this study, we evaluated the levels of Abs against IL-2, viral epitopes and interferon regulatory factor 5 (IRF5) in 140 RA patients and 137 healthy controls (HCs). Ab reactivity reached the highest levels for IRF5, EBV and IL-2 (56%, 44% and 39%, respectively) in RA with significantly lower values among HCs (7–9%, p <  0.0001), which suggests a possible cross-reaction between IRF5/EBV homologous antigens and shifts in T cell balance disrupted by anti-IL-2 Abs
Impairment of acquisition of intravenous cocaine self-administration by RNA-interference of dopamine D1-receptors in the nucleus accumbens shell
Microdialysis during i.v. drug self-administration (SA) have implicated nucleus accumbens (NAc) shell DA in cocaine and heroin reinforcement. However, this correlative evidence has not been yet substantiated by experimental evidence obtained by studying the effect of selective manipulation of NAc shell DA transmission on cocaine and heroin SA. In order to investigate this issue, DA D1a receptor (D1aR) expression was impaired in the NAc shell and core by locally infusing lentiviral vectors (LV) expressing specific D1aR-siRNAs (LV-siRNAs). Control rats were infused in the same areas with LV expressing GFP. Fifteen days later, rats were trained to acquire i.v. cocaine or heroin self-administration (SA). At the end of behavioral experiments, in order to evaluate the effect of LV-siRNA on D1aR expression, rats were challenged with amphetamine and the brains were processed for immunohistochemical detection of c-Fos and D1aR. Control rats acquired i.v. cocaine and heroin SA. Infusion of LV-siRNAs in the medial NAc shell reduced D1aR density and the number of c-Fos positive nuclei in the NAc shell, while sparing the core, and prevented the acquisition of cocaine, but not heroin SA. In turn, LV-siRNAs infusion in the core reduced D1aR density and the number of c-Fos positive nuclei in the same area, while sparing the shell, and failed to affect acquisition of cocaine. The differential effect of LV impairment of NAc shell D1aR on cocaine and heroin SA indicates that NAc shell DA acting on D1aR specifically mediates cocaine reinforcement
Early Diffusion of SARS-CoV-2 Infection in the Inner Area of the Italian Sardinia Island
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for the coronavirus disease 2019 (COVID-19) pandemic, which started as a severe pneumonia outbreak in Wuhan, China, in December 2019. Italy has been the first European country affected by the pandemic, registering a total of 300,363 cases and 35,741 deaths until September 24, 2020. The geographical distribution of SARS-CoV-2 in Italy during early 2020 has not been homogeneous, including regions severely affected as well as administrative areas being only slightly interested by the infection. Among the latter, Sardinia represents one of the lowest incidence areas likely due to its insular nature.
Methods: Next-generation sequencing of a small number of complete viral genomes from clinical samples and their virologic and phylogenetic characterization was performed.
Results: We provide a first overview of the SARS-CoV-2 genomic diversity in Sardinia in the early phase of the March–May 2020 pandemic based on viral genomes isolated in the most inner regional hospital of the island. Our analysis revealed a remarkable genetic diversity in local SARS-CoV-2 viral genomes, showing the presence of at least four different clusters that can be distinguished by specific amino acid substitutions. Based on epidemiological information, these sequences can be linked to at least eight different clusters of infection, four of which likely originates from imported cases. In addition, the presence of amino acid substitutions that were not previously reported in Italian patients has been observed, asking for further investigations in a wider population to assess their prevalence and dynamics of emergence during the pandemic.
Conclusion: The present study provides a snapshot of the initial phases of the SARS-CoV-2 infection in inner area of the Sardinia Island, showing an unexpected genomic diversity
Shelf-life of Halal fresh and minced beef meat packaged under modified atmosphere
The shelf-life of Halal fresh cut and minced beef meat, packaged under modified atmosphere (MAP) was evaluated. The microbial profile of the carcasses intended for cutting and mincing was investigated by detecting spoilage and pathogenic bacteria. Samples of diced meat (DM), marrowbones (MB), steaks (S) and minced meat (MM) were packaged in MAP (66.0% O2, 25.0% CO2 and 9.0% N2) and stored at +2 and +8°C. At 0, 7 and 14 days, gas composition of headspace was measured. Moreover, in all the samples colony count at 30°C, Enterobacteriaceae, lactic acid bacteria (LAB) and Pseudomonas spp. were determined. The carcasses contamination was in compliance with the criteria fixed by EC Reg. 2073/2005. Gas composition of the headspace changed significantly during the storage, mainly at +8°C, where a significant decrease of O2 (until 0.1-0.6%) and an increase of CO2 (until 81.0-89.0%) were recorded. This could be related to the level of LAB and Pseudomonas spp. Less significant changes were observed at +2°C. At 7 days of storage colony count, mean values were higher than >107 CFU/g in the samples at +8°C, and also at 14 days at +2°C, presumably due to the high levels of Pseudomonas spp., that was dominant at the end of the test. Overall, the microbial mean counts were higher than those detected in similar products packaged under vacuum. In order to extend the shelf-life of the fresh meat and meat preparations, differentiated gas mixtures, and particularly a higher percentage of CO2, could be employed
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