1,720,980 research outputs found
Microbicidal machanisms of human macrophages against Pseudomonas aeruginosa in healty subjects and cystic fibrosis patients
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Evaluation of antimicrobial activity of probiotic bacteria against salmonella enterica subsp. enterica serovar typhimurium 1344 in a common medium under different environmental conditions.
No full textRecurrent miscarriages in women not fulfilling classification criteria for antiphospholipid antibody syndrome
No full textObstetric antiphospholipid antibody syndrome (APS), is well defined by classification criteria. It is well known that women with APS should receive prophylactic anticoagulation therapy with subcutaneous low weight heparin all throughout pregnancy and in the first 6 weeks postpartum. However, the optimal treatment for pregnant women having positive anti-phospholipid antibodies, but not fulfilling classification criteria for APS is still unclear. In this retrospective study we report pregnancy outcomes of 10 patients affected by recurrent miscarriages and positive anti-cardiolipin or aβ2GP1 antibodies with titers ranging from 10 to 20 GPL/MPL demonstrated at least twice before pregnancy.Obstetric antiphospholipid antibody syndrome (APS), is well defined by classification criteria. It is well known that women with APS should receive prophylactic anticoagulation therapy with subcutaneous low weight heparin all throughout pregnancy and in the first 6 weeks postpartum. However, the optimal treatment for pregnant women having positive anti-phospholipid antibodies, but not fulfilling classification criteria for APS is still unclear. In this retrospective study we report pregnancy outcomes of 10 patients affected by recurrent miscarriages and positive anti-cardiolipin or aβ2GP1 antibodies with titers ranging from 10 to 20 GPL/MPL demonstrated at least twice before pregnancy
TRATTAMENTO ALTERNATIVO DELLA FIBROSI CISTICA: LA TERAPIA EPIGENETICA
No full textLa Fibrosi Cistica (FC) è una malattia autosomica recessiva causata da mutazioni nel gene “Cystic Fibrosis Transmembrane conductance Regulator” (CFTR) che codifica per un canale dello ione cloruro, espresso nelle cellule epiteliali di diversi tessuti. L’alterata funzionalità del CFTR determina, nei polmoni dei pazienti FC, una riduzione della secrezione del cloruro e un iperassorbimento dello ione sodio, per una mancata repressione del canale epiteliale per lo ione sodio (ENaC) (Gentzsch et al., J. Biol. Chem, 2010, 285:32227-32). ENaC è composto da tre subunità, α, ß e γ codificate rispettivamente dai geni SCNN1A, SCNN1B e SCNN1G. Studi precedenti suggeriscono che la metilazione del DNA possa controllare la trascrizione dei geni ENaC. Lo scopo del presente lavoro è quello di ridurre l’espressione dei geni ENaC mediante manipolazioni epigenetiche. Come modello di epitelio FC umano in coltura abbiamo utilizzato le cellule CFBE41o- (F508del / F508del) trattate con agenti ad azione ipermetilante sul DNA, come la SAM (S-adenosil-metionina) e ad azione ipercondensante sulla cromatina, come la curcumina (un inibitore dell’istone acetiltransferasi p300). L’espressione dei geni ENaC è stata valutata quantitativamente mediante real time PCR. Nelle cellule CFBE41o-, i trattamenti con SAM o curcumina riducono significativamente l’espressione dei geni SCNN1A e SCNN1B. Il trattamento combinato con SAM + curcumina determina una riduzione media dell’espressione dei geni SCNN1A e SCNN1B rispettivamente del 29% e 25% (ma fino al 36% e 60% in alcuni esperimenti). Inoltre, questi trattamenti non sembrano influenzare negativamente l’espressione del CFTR. Il gene SCNN1G risulta espresso a livelli troppo bassi perché la sua modulazione possa essere valutata in maniera attendibile. I nostri risultati suggeriscono che l’espressione dei geni SCNN1A e SCNN1B possa essere ridotta con l’utilizzo di trattamenti epigenetici e che approcci sinergici, che agiscono sia sulla metilazione del DNA sia sulla condensazione della cromatina, siano particolarmente efficienti. E’ in corso l’estensione di questi risultati anche a colture primarie di cellule epiteliali polmonari umane isolate da pazienti FC. Questo studio è finanziato dalla Fondazione per la ricerca sulla Fibrosi Cistica (Progetto #3/2012)
MMP-12 as a new marker of Stanford-A acute aortic dissection
No full textBackground. The study evaluated macrophage cytokines and macrophage metalloprotease (MMP)-12 levels in patients with Stanford-A acute aortic dissection (AAD) and in patients with critical carotid artery stenosis (CAS) compared with patients matched for age, sex, and traditional cardiovascular risk factors (RF). The aim was to identify possible early serum markers of risk for atherosclerotic complications. Materials and methods. We selected 65 patients: 23 AAD patients, 21 CAS patients, 21 RF, and 10 healthy subjects (HS). In each patient and control serum, levels of interleukin (IL)-6, IL-8, tumour necrosis factor (TNF)-alpha, monocyte chemoattractant protein (MCP)-1, vascular endothelial growth factor (VEGF), and MMP-12 were assessed by ELISA. Results. A significant increase of MMP-12, IL-6, and IL-8 levels in AAD versus CAS was found. Moreover, MMP-12 was shown to be significantly higher in AAD versus RF, but not in CAS versus RF. A significant increase of IL-6, IL-8, MCP-1, TNF-alpha, and VEGF levels was observed both in AAD and CAS versus RF. Conclusions. The results suggest that MMP-12 may be considered to be a specific marker of Stanford-A AAD. Furthermore, the study confirmed that in AAD and CAS macrophage cytokines play a key role in the progression of the atherosclerotic disease towards complications.Abstract
BACKGROUND:
The study evaluated macrophage cytokines and macrophage metalloprotease (MMP)-12 levels in patients with Stanford-A acute aortic dissection (AAD) and in patients with critical carotid artery stenosis (CAS) compared with patients matched for age, sex, and traditional cardiovascular risk factors (RF). The aim was to identify possible early serum markers of risk for atherosclerotic complications.
MATERIALS AND METHODS:
We selected 65 patients: 23 AAD patients, 21 CAS patients, 21 RF, and 10 healthy subjects (HS). In each patient and control serum, levels of interleukin (IL)-6, IL-8, tumour necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1, vascular endothelial growth factor (VEGF), and MMP-12 were assessed by ELISA.
RESULTS:
A significant increase of MMP-12, IL-6, and IL-8 levels in AAD versus CAS was found. Moreover, MMP-12 was shown to be significantly higher in AAD versus RF, but not in CAS versus RF. A significant increase of IL-6, IL-8, MCP-1, TN
Tobramycin-loaded biopolymeric nanoparticles for bacterial biofilms management
No full textThe aim of this work was to develop a polymeric drug delivery system able to improve the efficacy of antibiotics against P. aeruginosa (Pa) biofilms, the main respiratory pathogen in adult patients with cystic fibrosis.
Tobramycin (Tb)-loaded biopolymeric nanoparticles based on dextran sulphate (DS) and chitosan (CS) were prepared by ionotropic gelation. Tb content in CS/DS nanoparticles was measured by using an indirect spectrophotometric method. Tb in vitro release was studied by suspending a fixed amount of nanoparticles in PBS (pH 7.4) at 37°C and withdrawing samples at fixed time intervals. Antibiotic efficacy was tested on Pa biofilms and compared to free drug.
We optimized Tb entrapment in DS/CS nanoparticles, obtaining particles of 170 nm and with a drug loading of 400 μg/mg. Such preparations were able to release approximately 25% of their cargo in 60 hours.
Tb-loaded nanoparticles were tested on 2 days old P. aeruginosa biofilms and compared to free Tb. We obtained a reduction of the biofilm biomass using either free Tb or Tb-loaded nanoparticles, however the fraction of surviving bacteria was lower in samples treated with Tb-loaded nanoparticles in respect to those treated with an equal amount of free antibiotic.
It is well known that bacterial biofilms are less susceptible to antibiotic treatment compared to planktonic cells, although the mechanisms are still poorly understood. We showed that engineered nanoparticles with mucoadhesive properties, entrapping tobramycin, are more efficient in biofilm eradication than free drug
MMP-12 and TIMP Behavior in Symptomatic and Asymptomatic Critical Carotid Artery Stenosis
No full textObjective: The aim of this study was to evaluate the levels of matrix metalloproteinase-12 (MMP-12) and tissue inhibitors of metalloproteinases (TIMP)-1, TIMP-2, TIMP3, and TIMP-4 in patients with symptomatic and asymptomatic critical carotid artery stenosis (CAS). Methods: We enrolled 10 patients affected by symptomatic CAS within 12 hours from onset of stroke (S group) and 30 patients with asymptomatic CAS (CAS group); 31 patients matched for age, sex, and traditional cardiovascular risk factors were used as controls (RF group). Serum levels of MMP-12, TIMP-1, TIMP-2, TIMP-3, and TIMP-4 were assessed by Luminex. Results: MMP-12 levels were significantly higher both in the S and CAS groups than in the RF group (P <.001). We found a significant decrease of all TIMPs in the CAS group compared with the RF group, whereas a significant increase was observed in the S group compared with the CAS group. A significant increase of TIMP-3 and TIMP-4 levels was observed in the S group compared with all other groups. Conclusion: MMP-12 is related to critical CAS both symptomatic and asymptomatic, being mainly released in the late stage of plaque development. Moreover, we suggest that a specific pattern of matrix degrading enzyme inhibitors arises during the early phases of stroke
Stanford-A acute aortic dissection, inflammation, and metalloproteinases: a review
No full textAcute aortic dissection (AAD) is a life-threatening disease with an incidence of about 2.6-3.6 cases per 100,000/year. Depending on the site of rupture, AAD is classified as Stanford-A when the ascending aortic thoracic tract and/or the arch are involved, and Stanford-B when the descending thoracic aorta and/or aortic abdominal tract are targeted. It was recently shown that inflammatory pathways underlie aortic rupture in both type A and type B Stanford AAD. An immune infiltrate has been found within the middle and outer tunics of dissected aortic specimens. It has also been observed that the recall and activation of macrophages inside the middle tunic are key events in the early phases of AAD. Macrophages are able to release metalloproteinases (MMPs) and pro-inflammatory cytokines which, in turn, give rise to matrix degradation and neoangiogenesis. An imbalance between the production of MMPs and MMP tissue inhibitors is pivotal in the extracellular matrix degradation underlying aortic wall remodelling in dissections occurring both in inherited conditions and in atherosclerosis. Among MMPs, MMP-12 is considered a specific marker of aortic wall disease, whatever the genetic predisposition may be. The aim of this review is, therefore, to take a close look at the immune-inflammatory mechanisms underlying Stanford-A AAD
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