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Viola C. Scoffone Francesca Spadaro Claudia Udine Vadim Makarov Marco Fondi Renato Fani Edda De Rossi Giovanna Riccardi Silvia Buroni 《Antimicrobial agents and chemotherapy》2014,58(4):2415-2417
The discovery of new compounds that are able to inhibit the growth of Burkholderia cenocepacia is of primary importance for cystic fibrosis patients. Here, the mechanism of resistance to a new pyridine derivative already shown to be effective against Mycobacterium tuberculosis and to have good activity toward B. cenocepacia was investigated. Increased expression of a resistance-nodulation-cell division (RND) efflux system was detected in the resistant mutants, thus confirming their important roles in B. cenocepacia antibiotic resistance. 相似文献
33.
Patient‐ and family‐centred care in the intensive care unit: a challenge in the daily practice of healthcare professionals 下载免费PDF全文
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Stephen Zano Yasanandana S. Wijayasinghe Radhika Malik Joshua Smith Ronald E. Viola 《Journal of inherited metabolic disease》2013,36(1):1-6
Canavan disease (CD) is a fatal neurological disorder caused by defects in the gene that encodes for a critical metabolic enzyme. The enzyme aspartoacylase catalyzes the deacetylation of N-acetylaspartate to produce acetate required for fatty acid biosynthesis in the brain. The loss of aspartoacylase activity leads to the demyelination and disrupted brain development that is found in CD patients. Sixteen different clinical mutants of aspartoacylase have been cloned, expressed and purified to examine their properties and the relationship between enzyme properties and disease phenotype. In contrast to numerous cell culture studies that reported virtually complete loss of function, each of these purified mutant enzymes was found to have measureable catalytic activity. However, the activities of these mutants are diminished, by as little as three-fold to greater than 100-fold when compared to the native enzyme. Many of these mutated enzyme forms show decreased thermal stability and an increased propensity for denaturation upon exposure to urea, but only four of the 16 mutants examined showed both diminished thermal and diminished conformational stability. Significantly, each of these lower stability mutants are responsible for the more severe phenotypes of CD, while patients with milder forms of CD have aspartoacylase mutants with generally high catalytic activity and with either good thermal or good conformational stability. These results suggest that the loss of catalytic function and the accumulation of N-acetylaspartate in Canavan disease is at least partially a consequence of the decreased protein stability caused by these mutations. 相似文献
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Mathieu Wurtz Elisa Ruhland XuanLi Liu Izzie-Jacques Namer Viola Mazzoleni Dan Lipsker Daniel Keller Gilles Prvost David Gaucher 《Investigative ophthalmology & visual science》2021,62(1)
PurposeEndophthalmitis models have reported the virulent role of Panton-Valentine leucocidin (PVL) secreted by Staphylococcus aureus on the retina. PVL targets retinal ganglion cells (RGCs), expressing PVL membrane receptor C5aR. Interactions between PVL and retinal cells lead to glial activation, retinal inflammation, and apoptosis. In this study, we explored oxidative stress and retinal neurotransmitters in a rabbit retinal explant model incubated with PVL.MethodsReactive oxygen species (ROS) production in RGCs has been assessed with fluorescent probes and immunohistochemistry. Nuclear magnetic resonance (NMR) spectroscopy quantified retinal concentrations of antioxidant molecules and neurotransmitters, and concentrations of neurotransmitters released in the culture medium. Quantifying the expression of some pro-inflammatory and anti-inflammatory factors was performed using RT-qPCR.ResultsPVL induced a mitochondrial ROS production in RGCs after four hours’ incubation with the toxin. Enzymatic sources of ROS, involving nicotinamide adenine dinucleotide phosphate–oxidase and xanthine oxidase, were also activated after four hours in PVL-treated retinal explants. Retinal antioxidants defenses, that is, glutathione, ascorbate and taurine, decreased after two hours’ incubation with PVL. Glutamate retinal concentrations and glutamate release in the culture medium remained unaltered in PVL-treated retinas. GABA, glycine, and acetylcholine (Ach) retinal concentrations decreased after PVL treatment. Glycine release in the culture medium decreased, whereas Ach release increased after PVL treatment. Expression of proinflammatory and anti-inflammatory cytokines remained unchanged in PVL-treated explants.ConclusionsPVL activates oxidative pathways and alters neurotransmitter retinal concentrations and release, supporting the hypothesis that PVL could induce a neurogenic inflammation in the retina. 相似文献
38.
Anna Viola Daniela Pugliese Sara Renna Federica Furfaro Flavio Caprioli Renata D’Incà Fabrizio Bossa Stefano Mazza Giuseppe Costantino Massimo Claudio Fantini Gionata Fiorino Angela Alibrandi Ambrogio Orlando Alessandro Armuzzi Walter Fries 《Digestive and liver disease》2019,51(4):510-515
Background
Anti-TNF therapies infliximab (IFX), adalimumab (ADA), and golimumab (GOL) are approved for treating moderate to severe ulcerative colitis (UC). In UC, only the switch from IFX to ADA has been investigated, reaching no more than 10–43% remission rates at 12 months.Aim
Of the present study was to investigate disease outcome after a switch from subcutaneous (SC) agents to the intravenous (IV) agent (IFX).Methods
In this retrospective multicentre study, we analysed the charts of UC patients unresponsive/intolerant or with secondary loss of response (LOR) to ADA or GOL who were switched to IFX. We evaluated clinical response and remission together with adverse events at 3, 6, and 12 months follow-up.Results
Seventy-six patients were included; 38 patients started ADA and 38 started GOL for a mean therapy duration of 6?±?6 months. Indications for switch were adverse events in 3%, primary failure in 79%, and LOR in 18% of patients. Clinical remission was reached by 47%, 50%, and 77% of patients, respectively. Patients that switched for LOR did numerically, but not statistically, better than patients who switched for primary failure.Conclusions
Our data show a superior remission rate in SC to IV anti-TNF switch in UC compared to the IV to SC switch reported in literature. 相似文献39.
40.
Pieruzzi F Munforti C Di Blasio A Busca G Dadone V Zanchetti A Golin R 《Journal of hypertension》2002,20(10):2039-2045
OBJECTIVE: The aim of the present study was to evaluate the role of the renal nerves in the regulation of neuronal nitric oxide synthase (nNOS) gene expression in normotensive rats on different sodium balance. METHODS: Thirty-six male Sprague-Dawley rats were divided into six experimental groups combining three diets with different NaCl content (normal, 0.4%; low, 0.04%; or high, 4.0%), and bilateral renal denervation or sham denervation. After 7 days of dietary treatment, all rats were sacrificed and plasma renin activity (PRA) measured. The nNOS and renin messenger RNA (mRNA) levels in the renal cortex were determined by semiquantitative polymerase chain reaction. RESULTS: PRA was higher in animals with low sodium diet compared with those with standard diet, while it was lower in animals with high sodium diet. Renal denervation decreased PRA in normal and low sodium groups, while it did not alter the PRA values in the high sodium group. The nNOS gene expression significantly increased in rats fed with the low sodium diet compared with the standard diet group, and it significantly decreased in rats with the high sodium diet. Renal denervation significantly reduced nNOS mRNA levels in rats receiving the low sodium diet, but did not significantly influence nNOS mRNA in normal and high sodium groups. Renin mRNA was influenced by diets and denervation in a parallel way to nNOS mRNA. CONCLUSION: The renal nerves mediate the increase of renin and nNOS mRNA during sodium restriction, while the suppression of nNOS and renin gene expression during a sodium load is independent of the presence of the renal nerves. The parallel changes in renin and nNOS mRNA during different sodium intakes suggest that nNOS can be part of the complex, and still largely unclarified, macula densa mechanism of renin regulation. 相似文献