Differential Internalization of Amphotericin B - Conjugated Nanoparticles in Human Cells and the Expression of Heat Shock Protein 70

Although a variety of nanoparticles (NPs) functionalized with amphotericin B, an antifungal agent widely used in the clinic, have been studied in the last years their cytotoxicity profile remains elusive. Here we show that human endothelial cells take up high amounts of silica nanoparticles (SNPs) conjugated with amphotericin B (AmB) (SNP-AmB) (65.4 12.4 pg of Si per cell) through macropinocytosis while human fibroblasts internalize relatively low amounts (2.3 0.4 pg of Si per cell) because of their low capacity for macropinocytosis. We further show that concentrations of SNP-AmB and SNP up to 400 mg/mL do not substantially affect fibroblasts. In contrast, endothelial cells are sensitive to low concentrations of NPs (above 10 mg/mL), in particular to SNP-AmB. This is because of their capacity to internalize high concentration of NPs and high sensitivity of their membrane to the effects of AmB. Low-moderate concentrations of SNP-AmB (up to 100 mg/mL) induce the production of reactive oxygen species (ROS), LDH release, high expression of pro-inflammatory cytokines and chemokines (IL-8, IL-6, G-CSF, CCL4, IL-1b and CSF2) and high expression of heat shock proteins (HSPs) at gene and protein levels. High concentrations of SNP-AmB (above 100 ug/mL) disturb membrane integrity and kill rapidly human cells(60% after 5 h). This effect is higher in SNP-AmB than in SNP

Advances on Bacterial and Fungal Biofilms for the Production of Added-Value Compounds

Simple Summary The production of bio-based materials, including organic acids, antibiotics, enzymes, ethanol, and hydrogen, is generally done by the cultivation of suspended cells rather than using immobilized cells. However, several studies suggest the application of productive biofilms as a reliable alternative for biocatalysis, with many advantages over suspended-growth systems. This review gives an overview of the breakthrough in the application of biofilm platforms for the sustainable production of valuable compounds, with particular insight into the latest advances in the production of recombinant proteins. Productive biofilms are shown to improve production rates and product yields, demonstrating great potential for industrial applications. In recent years, abundant research has been performed on biofilms for the production of compounds with biotechnological and industrial relevance. The use of biofilm platforms has been seen as a compelling approach to producing fine and bulk chemicals such as organic acids, alcohols, and solvents. However, the production of recombinant proteins using this system is still scarce. Biofilm reactors are known to have higher biomass density, operational stability, and potential for long-term operation than suspended cell reactors. In addition, there is an increasing demand to harness industrial and agricultural wastes and biorefinery residues to improve process sustainability and reduce production costs. The synthesis of recombinant proteins and other high-value compounds is mainly achieved using suspended cultures of bacteria, yeasts, and fungi. This review discusses the use of biofilm reactors for the production of recombinant proteins and other added-value compounds using bacteria and fungi

CARD15 Mutations and Perianal Fistulating Crohn’s Disease: Correlation and Predictive Value of Antibiotic Response

BACKGROUND: CARD15 mutations alter bowel immunity and increase susceptibility to Crohn's disease (CD). However, the relation between these mutations and Crohn's perianal fistulas has not been fully clarified. AIMS: To assess whether CARD15 mutations are associated with risk of developing Crohn's perianal fistulas and whether these mutations are predictors of the response of perianal fistulas to antibiotics. METHODS: CARD15 mutations were investigated in 203 consecutive CD patients. Presence/absence of history of perianal fistula was recorded. Patients with history of perianal fistula were divided into two groups (with/without CARD15 mutations), and response to antibiotics was evaluated in both groups. RESULTS: Of the 203 patients, 60 (29.6%) showed at least one CARD15 mutation and 55 (27.1%) had history of perianal fistula. History of perianal fistula was identified in 13 (21.7%) patients with mutations and in 42 (29.4%) patients without mutations (P = 0.260). Mean age at diagnosis of first perianal fistula was similar in patients with/without CARD15 mutations (28.7 +/- 9.8 versus 29.7 +/- 10.1 years, P = 0.758). Average time between disease onset and diagnosis of first perianal fistula was also similar in the two groups (4.6 +/- 5.1 versus 5.0 +/- 5.9 years, P = 0.816). Response of perianal fistulas to antibiotics (metronidazole alone or combined with ciprofloxacin) was significantly higher in patients without CARD15 mutations (7.7% versus 40.5%, P = 0.041). CONCLUSIONS: In CD, CARD15 mutations are not associated with risk of developing perianal fistulas or with time of their outbreak. Nevertheless, patients with perianal fistulas and CARD15 mutations showed worse response to antibiotics

Cerebral Venous Thrombosis Imagiologic Features in a Pregnant Woman

A trombose venosa cerebral (TVC) é uma doença relativamente rara mas grave, potencialmente reversível com diagnóstico atempado e terapêutica médica adequada. A gravidez e o puerpério são um factor predisponente de TVC, que é responsável por 6% das causas de morte materna. As manifestações clínicas dependem da localização, extensão do trombo, bem como da rede de colaterais existente. Apresentamos o caso duma doente do sexo feminino, 33 anos, grávida de 13 semanas que recorreu ao serviço de urgência por quadro de cefaleias e cujo estudo por Ressonância Magnética revelou aspectos compatíveis com doença venosa oclusiva subtotal do seio longitudinal superior em fase aguda. A propósito deste caso discutimos as manifestações imagiológicas da trombose venosa dural na fase aguda

Leadless Pacemaker Implantation Via Azygos Vein in a Patient with Absence of the Hepatic Segment of the Inferior Vena Cava

info:eu-repo/semantics/publishedVersio

Chiropractic Manipulation: Reasons for Concern?

Chiropractic's popularity is rising among the general population. Moreover, few studies have been conducted to properly evaluate its safety. We report three cases of serious neurological adverse events in patients treated with chiropractic manipulation. The first case is a 41 years old woman who developed a vertebro-basilar stroke 48 h after cervical manipulation. The second case represents a 68 years old woman who presented a neuropraxic injury of both radial nerves after three sessions of spinal manipulation. The last case is a 34 years old man who developed a cervical epidural haematoma after a chiropractic treatment for neck pain. In all three cases there were criteria to consider a causality relation between the neurological adverse events and the chiropractic manipulation. The described serious adverse events promptly recommend the implementation of a risk alert system

Effect of Carvacrol on Salmonella Saintpaul Biofilms on Stainless Steel Surface

Purpose: To evaluate the effect of carvacrol against Salmonella Saintpaul biofilms on stainless steel surface.Methods: The effects of carvacrol on planktonic cells were evaluated by determining the minimum inhibitory concentration and minimal bactericidal concentration. The action of carvacrol on Salmonella Saintpaul biofilms on stainless steel surface was evaluated on established biofilm and on biofilm formation by counting the number of bacterial cells that adhered to the surface using scanning electron microscopy.Results: The antimicrobial activity of carvacrol in planktonic cells of Salmonella Saintpaul was observed. The highest inhibitory effect of carvacrol was observed on biofilm formation at different subinhibitory concentrations.Conclusion: Carvacrol reduced the number of bacterial cells that adhered to stainless steel surface, making it a potential compound for Salmonella Saintpaul control.Keywords: Salmonella spp, Biofilm, Planktonic cells, Carvacrol, Stainless stee