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.

Structure-function relationships in a glycosyltransferase, a phosphatase and an oxidoreductase

Dissertation presented to obtain the Ph.D degree in Biochemistry

Atheroembolic Renal Disease As a Cause of Allograft Primary Non-Function

Atheroembolic renal disease, also referred to as cholesterol crystal embolization, is a rare cause of renal failure, secondary to occlusion of renal arteries, renal arterioles and glomerular capillaries with cholesterol crystals, originating from atheromatous plaques of the aorta and other major arteries. This disease can occur very rarely in kidney allografts in an early or a late clinical form. Renal biopsy seems to be a reliable diagnostic test and cholesterol clefts are the pathognomonic finding. However, the renal biopsy has some limitations as the typical lesion is focal and can be easily missed in a biopsy fragment. The clinical course of these patients varies from complete recovery of the renal function to permanent graft loss. Statins, acetylsalicyclic acid, and corticosteroids have been used to improve the prognosis. We report a case of primary allograft dysfunction caused by an early and massive atheroembolic renal disease. Distinctive histology is presented in several consecutive biopsies. We evaluated all the cases of our Unit and briefly reviewed the literature. Atheroembolic renal disease is a rare cause of allograft primary non -function but may become more prevalent as acceptance of aged donors and recipients for transplantation has become more frequent.

Gain-of-Function Mutations in IFIH1 Cause a Spectrum of Human Disease Phenotypes Associated with Upregulated Type I Interferon Signaling

The type I interferon system is integral to human antiviral immunity. However, inappropriate stimulation or defective negative regulation of this system can lead to inflammatory disease. We sought to determine the molecular basis of genetically uncharacterized cases of the type I interferonopathy Aicardi-Goutières syndrome, and of other patients with undefined neurological and immunological phenotypes also demonstrating an upregulated type I interferon response. We found that heterozygous mutations in the cytosolic double-stranded RNA receptor gene IFIH1 (MDA5) cause a spectrum of neuro-immunological features consistently associated with an enhanced interferon state. Cellular and biochemical assays indicate that these mutations confer a gain-of-function - so that mutant IFIH1 binds RNA more avidly, leading to increased baseline and ligand-induced interferon signaling. Our results demonstrate that aberrant sensing of nucleic acids can cause immune upregulation.

Dor à Palpação da Tiróide

A 37-years-old woman, complaining of fever, malaise, myalgia, sore throat and dysphagia lasting for 15 days, had been taking antibiotics and paracetamol for 7 days, without symptoms' improvement. The clinical examination revealed hyperaemic oropharynx and enlarged, painful thyroid. Further exams showed increased analytic inflammatory serum parameters as well as thyrotoxicosis. The thyroid gland had heterogeneous echostructure, with markedly hypoechoic areas and significant capsular oedema as well as decreased radionuclide uptake in the scintigraphy. Both symptoms and imaging improved with paracetamol and ibuprofen. Thyroid gland function normalized in two months. The patient remains in follow-up. This case reports the clinical features of subacute or De Quervain's thyroiditis. The differential medical approach to the patient with painful thyroid palpation is discussed. The diagnosis is essentially clinic, highlighting the importance of a rigorous physical exam. These patients' follow-up is required, considering the clinical and analytic progression.

Liver function evaluation in leptospirosis with colloidal gold 1 9 8 Au

Eight patients with leptospirosis were studied with colloidal gold 1 9 8 Au. The radiocolloidal hepatic distribution was altered, presenting a non-homogeneous tiver concentration in seven cases, and a minute to moderate splenic visualization in five. Two patients presented doubtful splenic image, and one seemed to be normal. Liver scanning with colloidal gold 1 9 8 Au is demonstra ted to be a good liver function test.

The compliance function in banking: Perspective and future in the age of globalization

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics

Differential exploitation of cashew - a low conflict crop - by sympatric humans and chimpanzees

Modification of natural areas by human activities mostly has a negative impact on wildlife by increasing the geographical and ecological overlap between people and animals. This can result in escalating levels of competition and conflict between humans and wildlife, for example over crops. However, data on specific crops and crop parts that are unattractive to wildlife yet important for human livelihoods are surprisingly scarce, especially considering their potential application to reducing crop damage by wildlife. Here we examine the co-utilization of a nationally important and spatially abundant cash crop, cashew Anacardium occidentalis, by people and chimpanzees Pan troglodytes verus inhabiting a forested–agricultural matrix in Cantanhez National Park in Guinea-Bissau. In this Park people predominantly harvest the marketable cashew nut and discard the unprofitable fruit whereas chimpanzees only consume the fruit. Local farmers generally perceive a benefit of raiding by chimpanzees as they reportedly pile the nuts, making harvesting easier. By ensuring that conflict levels over crops, especially those with high economic importance, remain low, the costs of living in proximity to wildlife can potentially be reduced. Despite high levels of deforestation associated with cashew farming, these findings point to the importance of cashew as a low-conflict crop in this area.

Evaluation of platelet number and function and fibrinogen level in patients bitten by snakes of the Bothrops genus

Platelet function and plasma fibrinogen levels were evaluated in 14 patients, 10 males and 4females, aged 13-59years bitten by Bothrops genus snakes. There was a statistical difference (p < 0.05) among plasma fibrinogen levels evaluated 24 and 48 hours after envenomation. There was a tendency towards normalization after 48 hours of treatment. The low platelet number was clear in 24-48 hour evaluations with a tendency towards normalization after 48 hours of treatment (p<0.05). Fibrinogen levels and fibrin degradation product (FDP) levels appeared to be altered in 83.33% of patients evaluated. The authors suggest that platelet hypoaggregation is related to decreased fibrinogen and increased FDP levels.

Micropollutant bioremoval in wastewater treatment systems: from microbial population structure to function

Dissertation presented to obtain the Ph.D degree in Biology

Avian infectious bronchitis virus (IBV): differential pathological and immunological profiles of two Brazilian variants.

2015

How to improve supply chain performance of a specialized retailer: Managing landed costs of Zippy’s global supply chain

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics

STRUCTURE-FUNCTION ANALYSIS OF MULTI-COPPER OXIDASES

Dissertation presented to obtain the Ph.D degree in Biochemistry, Structural Biochemistry

Dissecting the function of the SpoIIIJ and YqjG membrane protein insertases during bacterial spore development

Dissertation presented to obtain the Ph.D degree in Biology, Microbial Biology

Regulation and function of the cell wall polymer lipoteichoic acid in staphylococcus aureus

A thesis submitted for the Degree of Master in Medical microbiology